The human body contains over 200 cell types that all originate from a single fertilized egg cell. Cells differentiate and specialize to perform specific functions. The basic components of cells are the nucleus, which houses the DNA, and the cytoplasm, which contains organelles. The plasma membrane encloses the cell and regulates what enters and exits. Cells communicate through signaling molecules that bind receptors and trigger intracellular signal transduction pathways. Endocytosis and exocytosis allow materials to be transported into and out of cells while maintaining membrane integrity. The nucleus contains DNA and directs cellular activities through gene expression.
2. The human organism presents about 200 different cell
types, all derived from the zygote, the single cell formed
by fertilization of an oocyte with a spermatozoon.
īĸ During their specialization process, called cell
differentiation, the cells synthesize specific proteins,
change their shape, and become very efficient in
specialized functions.
īĸ The body's cells can experience both normal and
pathological conditions and the same cell type can
exhibit different characteristics and behaviors in different
regions and circumstances
īĸ
4. īĸ
The cell is composed of two basic parts:
Cytoplasm and
Nucleus.
īĸ
Individual cytoplasmic components are usually not clearly
distinguishable in common hematoxylin-and-eosinâstained
preparations.
īĸ
The nucleus, appears intensely stained dark blue or black.
īĸ
The cytoplasm is composed of a fluid component, or cytosol, which
containes metabolically active structures, the organelles, which can
be membranous (such as mitochondria) or non-membranous protein
complexes (such as ribosomes and proteasomes).
7. īĸ
The outermost component of the cell, separating the
cytoplasm from its extracellular environment, is the
Plasma membrane or Plasmalemma.
īĸ
All eukaryotic cells are enveloped by a limiting
membrane composed of phospholipids, cholesterol,
proteins, and chains of oligosaccharides covalently
linked to phospholipid and protein molecules.
īĸ
Membranes range from 7.5 to 10 nm in thickness and
visible only in the electron microscope.
8.
9. īĸ
With electron microscopy, the plasmalemma and, all other organellar
membranes appears a trilaminar structure after fixation in osmium
tetroxide.
īĸ
Because all membranes have this appearance, the 3-layered structure was
designated the unit membrane.
īĸ
Membrane phospholipids, such as phosphatidylcholine (lecithin),
consist of two non-polar (hydrophobic or water-repelling) long-chain
fatty acids linked to a charged polar (hydrophilic or water-attracting)
head group.
īĸ
Membrane phospholipids are most stable when organized into a double
layer (bilayer) with their hydrophobic fatty acid chains directed toward
the middle away from water and their hydrophilic polar heads directed
outward to contact water on both sides.
10. īĸ
Cholesterol molecules insert among the close packed the phospholipid
fatty acids nearly a 1:1 ratio , restricting their movement, and thus
modulate the fluidity and movement of all membrane components.
īĸ
The lipid composition of each half of the bilayer is different.
īĸ
In red blood cells phosphatidylcholine and sphingomyelin are more
abundant in the outer half of the membrane, whereas phosphatidylserine
and phosphatidylethanolamine are more concentrated in the inner half.
īĸ
Some of the lipids, known as glycolipids, possess oligosaccharide chains
that extend outward from the surface of the cell membrane and thus
contribute to the lipid asymmetry.
11.
12.
13. īĸ
Proteins, are major molecular constituent of membranes, can be
divided into two groups.
Integral proteins :
o Incorporated within the lipid bilayer.
o Some integral proteins span the membrane one or more times,
from one side to the other, they are called one-pass or
multipass transmembrane proteins.
Peripheral proteins :
exhibit a looser association with one of the two
membrane surfaces.
14. īĸ
īĸ
īĸ
īĸ
With freeze-fracture electron microscope studies of membranes
show that many integral proteins are only partially embedded in the
lipid bilayer and protrude from either the outer or inner surface.
Transmembrane proteins are large enough to extend across the two
lipid layers and may protrude from both membrane surfaces.
The carbohydrate moieties of the glycoproteins and glycolipids
project from the external surface of the plasma membrane; they are
important components of specific molecules called receptors that
participate in important interactions such as cell adhesion,
recognition, and response to protein hormones.
As with lipids, the distribution of membrane proteins is different in
the two surfaces of the cell membranes. Therefore, all membranes in
the cell are asymmetric.
15. īĸ
īĸ
īĸ
īĸ
īĸ
Integration of the proteins within the lipid bilayer is mainly the
result of hydrophobic interactions between the lipids and nonpolar
amino acids present on the outer region of the proteins.
Some membrane proteins are not bound rigidly in place and are able
to move within the plane of the cell membrane.
unlike lipids, most membrane proteins are restricted in their lateral
diffusion by attachment to cytoskeletal components.
In most epithelial cells, tight junctions also restrict lateral diffusion
of unattached transmembrane proteins and outer layer lipids to
specific membrane domains.
The mosaic disposition of membrane proteins and the fluid nature of
the lipid bilayer and led to the well-established fluid mosaic model
for membrane structure.
16.
17. Functions of plasmalemma :
īĸ
A selective barrier.
īĸ
To keep constant the ion content of cytoplasm.
īĸ
Specific recognition and regulatory functions.
18. GLYCOCALYX
īĸ
īĸ
īĸ
īĸ
īĸ
With the EM the external surface of the cell shows a fuzzy
carbohydrate-rich region called the glycocalyx.
This layer is made of carbohydrate chains linked to membrane
proteins and lipids and of cell-secreted glycoproteins and
proteoglycans.
The glycocalyx has a role in cell recognition and attachment to other
cells and to extracellular molecules.
Some ions, such as Na+, K+, and Ca2+, cross the cell membrane by
passing through integral membrane proteins.
This can involve passive diffusion through ion channels or active
transport via ion pumps using energy from the breakdown of
adenosine triphosphate (ATP).
19. ENDOCYTOSIS
īĸ
Bulk uptake of material also occurs across the plasma membrane in
a general process called endocytosis, which involves folding and
fusion of this membrane to form vesicles which enclose the material
transported.
īĸ
Cells show three general types of endocytosis.
1. Phagocytosis
2. Fluid-phase Endocytosis
3.Receptor-mediated Endocytosis
20. Phagocytosis :
o
o
o
Certain white blood cells, such as macrophages and neutrophils, are
specialized for engulfing and removing particulate matter such as
bacteria, protozoa, dead cells, and unneeded extracellular
constituents.
When a bacterium becomes bound to the surface of a neutrophil,
cytoplasmic processes of the cell are extended and ultimately
surround the bacterium.
The membranes of these processes meet and fuse, enclosing the
bacterium in an intracellular vacuole, a phagosome.
22. Fluid-phase Endocytosis :
īĸ
In fluid-phase pinocytosis , smaller invaginations of the cell
membrane form and entrap extracellular fluid and anything it has in
solution.
īĸ
Pinocytotic vesicles (about 80 nm in diameter) pinch off inwardly
from the cell surface.
īĸ
In most cells such vesicles usually fuse with lysosomes.
24. Receptor-mediated Endocytosis :
īĸ Receptors for many substances, such as low-density
lipoproteins and protein hormones, are integral proteins of the
cell membrane.
īĸ Binding of the ligand (a molecule with high affinity for a
receptor) to its receptor causes widely dispersed receptors to
aggregate in special membrane regions called coated pits.
īĸ The electron-dense coating on the cytoplasmic surface of the
membrane is composed of several polypeptides, the major one
being Clathrin.
īĸ In a developing coated pit clathrin molecules, forming that
region of cell membrane into a cage-like invagination that is
pinched off into the cytoplasm, forming a coated vesicle
carrying the ligand and its receptor.
27. In endocytotic processes, the vesicles or vacuoles
produced quickly enter and fuse with the endosomal
compartment, a dynamic system of membranous
vesicles and tubules located in the cytoplasm near the
cell surface (early endosomes) or deeper in the
cytoplasm (late endosomes).
īĸ The clathrin molecules separated from the coated
vesicles recycle to the cell membrane to participate in
the formation of new coated pits.
īĸ The membrane of endosomes contains ATP-driven H+
pumps that acidify their interior.
īĸ
28. While phagosomes and pinocytotic vesicles soon fuse with
lysosomes, molecules penetrating the endosomal
compartment after receptor-mediated endocytosis may take
more than one pathway.
īĸ The acidic pH of early endosomes causes many ligands to
uncouple from their receptors, after which the two
molecules are sorted into separate vesicles.
īĸ The receptors may be returned to the cell membrane to be
reused.
īĸ The ligands typically are transferred to late endosomes.
īĸ Some ligands are returned to the extracellular milieu with
their receptors and both are used again.
īĸ Late endosomes most commonly fuse with lysosomes for
degradation of their contents.
īĸ
29.
30. EXOCYTOSIS
In exocytosis a membrane-limited cytoplasmic vesicle
fuses with the plasma membrane, resulting in the release
of its contents into the extracellular space without
compromising the integrity of the plasma membrane.
īĸ Often exocytosis of stored products from epithelial cells
occurs specifically at the apical domains of cells, such as
in the exocrine pancreas and the salivary glands.
īĸ The fusion of membranes during exocytosis is a highly
regulated process involving interactions between several
specific membrane proteins.
īĸ Exocytosis is triggered in many cells by transient
increase in cytosolic Ca2+.
īĸ
31. īĸ
During endocytosis, portions of the cell membrane
become endocytotic vesicles; during exocytosis, the
membrane is returned to the cell surface.
īĸ
This process of membrane movement and recycling is
called membrane trafficking.
īĸ
Trafficking and sorting of membrane components occur
continuously in most cells and are not only crucial for
cell maintenance but also physiologically important in
processes such as reducing blood lipid levels.
32. SIGNAL RECEPTION AND
TRANSDUCTION
īĸ
Cells in a multicellular organism need to communicate with one
another to regulate their development into tissues, to control
their growth and division, and to coordinate their functions.
īĸ
Soluble extracellular signaling molecules bind receptor proteins
only found on their target cells.
īĸ
Each cell type in the body contains a distinctive set of receptor
proteins that enable it to respond to a complementary set of
signaling molecules in a specific, programmed way.
33. Signaling can take different routes:
Endocrine signaling:
īĸ the signal molecules (called hormones) are carried in the blood to target
cells throughout the body.
Paracrine signaling :
īĸ the chemical mediators are rapidly metabolized so that they act only on
local cells very close to the source.
Synaptic signaling :
īĸ a special kind of paracrine interaction, neurotransmitters act only on
adjacent cells through special contact areas called synapses.
Autocrine signaling :
īĸ signals bind receptors on the same cell type that produced the messenger
molecule.
34. īĸ
īĸ
īĸ
īĸ
īĸ
Hydrophilic signaling molecules :
including most hormones, local chemical mediators (paracrine
signals), and neurotransmitters activate receptor proteins on the surface
of target cells.
These receptors, often transmembrane proteins, relay information to a
series of intracellular intermediaries that ultimately pass the signal (first
messenger) to its final destination in either the cytoplasm or the nucleus
in a process called Signal transduction.
One of the intermediary proteins, the G proteins, binds guanine
nucleotides and acts on other membrane-bound intermediaries called
effectors which propagate the signal further into the cell.
Effector proteins are usually ion channels or enzymes that generate large
quantities of small second messenger molecules, such as 1,2diacyglycerol (DAG), cyclic adenosine monophosphate (cAMP), and
inositol 1,4,5-triphosphate (IP3).
The ions or second messengers diffuse through the cytoplasm,
amplifying the first signal and triggering a cascade of molecular
reactions that lead to changes in gene expression or cell behavior.
35.
36. MEDICAL APPLICATION
Several diseases have been caused by defective receptors.
īĸ Pseudohypoparathyroidism and a type of Dwarfism are
caused by nonfunctioning parathyroid and growth hormone
receptors.
īĸ In these two conditions the glands produce the respective
hormones, but the target cells do not respond because they
lack normal receptors.
īĸ
37. Hydrophobic signaling molecules :
such as small steroid and thyroid hormones, bind
reversibly to carrier proteins in the plasma for transport
through the body.
īĸ Such hormones are lipophilic and once released from their
carrier proteins, they diffuse directly through the plasma
membrane lipid bilayer of the target cell and bind to specific
intracellular receptor proteins.
īĸ With many steroid hormones, receptor binding activates that
protein, enabling the complex to move into the nucleus and
bind with high affinity to specific DNA sequences.
īĸ This generally increases the level of transcription from
specific genes.
īĸ
40. The nucleus contains a blueprint for all cell structures
and activities encoded in the DNA of the chromosomes .
īĸ Nucleus is the site of deoxyribonucleic acid (DNA)
replication and transcription of DNA into precursor
ribonucleic acid (RNA)molecules.
īĸ It contains all of the enzymes required for replication
and repair of newly synthesized DNA, as well as for
transcription and processing of precursor RNA
molecules.
īĸ It is enclosed by the nuclear envelope and contains the
nuclear lamina, nucleolus, and chromatin
īĸ
41. Nuclear envelope :
īĸ
The nuclear envelope is a double membrane
containing pores that are approximately 90 nm in
diameter.
īĸ
The outer nuclear membrane is continuous with
the endoplasmic reticulum.
42.
43.
44.
45.
46. Nuclear Lamina :
īĸ
The nuclear lamina is a latticelike network of
proteins that include lamins.
īĸ
Lamins attach chromatin to the inner membrane
of the nuclear envelope and participate in the
breakdown and reformation of the nuclear
envelope during the cell cycle.
īĸ
Phosphorylation of the lamins, (by lamin kinase)
during prophase of mitosis initiates nuclear
disassembly into small vesicles.
47. Nuclear Lamina
Functions:
Maintenance of nuclear shape
Spatial organization of nuclear pores within nuclear membrane
Regulation of transcription
Anchoring of interphase heterochromatin
DNA replication.
51. Nucleolus :
īĸ
The nucleolus is responsible for ribosomal RNA
(rRNA) synthesis and ribosome assembly.
īĸ
It contains three morphologically distinct zones:
âĸ Granular zoneâfound at the periphery; contains
ribosomal precursor particles in various stages of
assembly.
âĸ Fibrillar zoneâcentrally located; contains ribonuclear
protein fibrils.
âĸ Fibrillar centerâcontains DNA that is not being
transcribed.
52. Nucleolus :
īĸ
The nucleolus is responsible for ribosomal RNA
(rRNA) synthesis and ribosome assembly.
īĸ
It contains three morphologically distinct zones:
âĸ Granular zoneâfound at the periphery; contains
ribosomal precursor particles in various stages of
assembly.
âĸ Fibrillar zoneâcentrally located; contains ribonuclear
protein fibrils.
âĸ Fibrillar centerâcontains DNA that is not being
transcribed.
53.
54. Chromatin :
Chromatin is a complex of DNA, histone proteins, and nonhistone
proteins.
âĸ DNAâa double-stranded helical molecule that carries the genetic
information of the cell.
īĸ It exists in three conformations: B DNA, Z DNA, and A DNA.
âĸ Histone proteinsâpositively charged proteins enriched with lysine
and arginine residues.
īĸ They are important in forming two types of structures in chromatin:
nucleosomes and solenoid fibers.
īĸ The nucleosomes are the basic repeating units of the chromatin
fiber, having a diameter of approximately 10 nm.
âĸ Nonhistone proteinsâinclude enzymes involved in nuclear functions
such as replication, transcription, DNA repair, and regulation of
chromatin function.
īĸ They are acidic or neutral proteins.
58. Forms of Chromatin :
âĸ Heterochromatin :
highly condensed and transcriptionally inactive.
īĸ In a typical eukaryotic cell, approximately 10% of the
chromatin is heterochromatin.
âĸ Euchromatin :
a more extended form of DNA, which is
potentially transcriptionally active.
īĸ In a typical cell, euchromatin accounts for approximate
90%of the total chromatin, although only about 10% is
being actively transcribed.
61. RIBOSOMES
Ribosomes are composed of rRNA and protein. They
consist of large (60S) and small (40S) subunits.
īĸ Ribosomes are assembled in the nucleus and transported
to the cytoplasm through the nuclear pores.
īĸ The large ribosomal subunits are synthesized in the
nucleolus, whereas the small subunits are synthesized in
the nucleus.
Polysomes :
īĸ Ribosomes often form polysomes, which consist of a
single messenger RNA (mRNA) that is being translated
by several ribosomes at the same time.
īĸ The ribosomes move on the mRNA from the 5' end
towards 3' end.
īĸ The two ribosomal subunits associate on the mRNA,
with the small subunit binding first
īĸ
62.
63. Forms of Ribosomes :
Ribosomes exist in two forms:
âĸ Free polysomes : are the site of synthesis for
proteins destined for the nucleus, peroxisomes, or
mitochondria.
âĸ Membrane-associated polysomes : are the site of
synthesis of secretory proteins, membrane
proteins, and lysosomal enzymes.
64. ENDOPLASMIC RETICULUM
The endoplasmic reticulum exists in two forms, rough
endoplasmic reticulum (RER) and smooth endoplasmic
reticulum (SER).
īĸ Rough Endoplasmic Reticulum :
īĸ RER is a single, lipid bilayer continuous with the outer
nuclear membrane.
īĸ It is organized into stacks of large flattened sacs called
cisternae that are studded with ribosomes on the cytoplasmic
side.
īĸ RER snthesize poteins that are destined for the Golgi
apparatus, secretion, the plasma membrane, and lysosomes.
īĸ RER is very prominent in cells that are specialized in the
synthesis of proteins destined for secretion
(eg : pancreatic acinar cells).
īĸ
69. Smooth Endoplasmic Reticulum :
īĸ
SER is a network of membranous sacs, vesicles, and
tubules continuous with the RER, but lacking ribosomes.
īĸ
SER contains enzymes involved in the synthesis of
phospholipids, triglycerides, and sterols
70. Functions of SER :
o
o
o
o
Detoxification Reactions :
Hydroxylation.
Conjugation.
Glycogen Degradation and Gluconeogenesis
Reactions in Lipid Metabolism
Sequestration and Release of Calcium Ions
72. GOLGI APPARATUS
īĸ
The Golgi apparatus consists of disc-shaped smooth
cisternae that are assembled in stacks (dictyosomes), and
associated with numerous small membrane-bound vesicles.
īĸ
The Golgi apparatus has two distinct faces:
âĸ The cis (forming) face is associated with the RER.
âĸ The trans (maturing) face is often oriented toward the
plasma membrane.
īĸ
Important in glycosylation, phosphorylation, sulfation, etc.
Takes part in synthesis, concentration & storage of
secretory products.
īĸ
73.
74. Functions of the Golgi Apparatus :
Proteins and Lipids
īĸ The Golgi apparatus is the site of post trauslational
modification and sorting of newly synthesized proteins
and lipids.
Glycoproteins
īĸ Further modification of the carbohydrate moiety of
glycoproteins produces complex and hybrid
oligosaccharide chains.
īĸ This determines which proteins remain in the Golgi
apparatus or leave the Golgi apparatus to become
secretory proteins, lysosomal proteins, or part of the
plasma membrane.
īĸ Two diseases are caused by a breakdown in this process,
I-cell disease and hyperproinsulinemia
75.
76.
77.
78. MEDICAL APPLICATION
Hyperprolnsulinemia :
Hyperprolnsulinemia is characterized by elevated levels of
proinsulin in the serum resulting from the failure of a
peptidase to cleave proinsulin to insulin and C-peptide in the
golgi apparatus.
I-Cell Disease :
Phosphorylation of mannose in glycoproteins targets proteins
to lysosomes.
īĸ Phosphate is added in a two-step sequence of reactions that
are catalyzed by N-acetylglucosamine-phosphotransferase
and N-acetylglucosaminidases.
īĸ A deficiency in N-acetylglucosamine-phosphotransferase
results In I-cell dieease .
79. LYSOSOMES
īĸ
Lysosomes are spherical membrane-enclosed organelles
that are contain enzymes required for intracellular
digestion.
Lysosomes consist of two forms :
âĸPrimary lysosomes have not yet acquired the materials to
be digested.
īĸ They are formed by budding from the trans side of the
Golgi apparatus.
âĸSecondary lysosomes are formed by the fusion of the
primary lysosome with the substrate to be degraded and
have contents that are in various stages of degradation
īĸ
80.
81.
82.
83. īĸ
âĸ
Lysosomes contain approximately 60 hydrolytic
enzymes.
All lysosomal enzymes are acid hvdrolases, with
optimal activity at a pH of approximately 5.0.
The synthesis of the lysosomal hydrolases occurs
in RER.
īĸ All hydrolasea are transferred to the Golgi
apparatus where they are modified and packaged
into lysosomes.
īĸ
84. MEDICAL APPLICATION
Glycogen-Storage Disease Type II (Pompe Disease) :
īĸ an autosomal recessive disorder that results from the deficiency
of acid alpha-glucosidase, a lysosomal hydrolase , is required
for the degradation of a small percentage (1-3%) of cellular
glycogen.
īĸ Because the main pathway for glycogen degradation is not
deficient in glycogen-storage disease type II disease, energy
production is not impaired, and hypoglycemia does not occur.
īĸ However, the deficiency of this enzymatic activity results in the
accumulation of structurally normal glycogen in lysosomes and
cytoplasm in affected individuals.
īĸ Excessive glycogen storage within lysosomes may interrupt
normal functioning of other organelles and leads to cellular
injury. In turn, this leads to enlargement and dysfunction of the
entire organ involved (eg, cardiomyopathy).
85. RESIDUAL BODIES
âĸLysosomes containing
indigestible compounds
are called residual
bodies.
âĸThe indigestible
compounds are usually
exocytosed.
âĸThe unreleased
indigestible compounds
in long-living cells
appear as lipofuscins or
aging pigments.
88. AUTOPHAGOSOMES
Primary Liposomes fuse
with membrane-bound
organelles or a portion
of cytoplasm to form
autophagosomes.
īĸ
Autolysis occurs when
lysosomes rupture and
destroy the cell itself.
īĸ
89. PEROXISOMES
īĸ
Peroxisomes are a heterogeneous group of small,
spherical organelles with a single membrane.
Functions:
Synthesis and degradation of hydrogen peroxide.
īĸ Oxidation of very long chain fatty acids (> C24).
īĸ Phospholipid exchange.
īĸ Bile acid synthesis.
īĸ
91. MEDICAL APPLICATION
Peroxisome Deficiency :
Several genetic diseases are associated with the impairment
or absence of peroxisomes.
īĸ These patients fail to oxidize very long chain fatty acids and
accumulate bile acid precursors.
īĸ
īĸ
The four most common disorders are:
âĸ Zellweger (cerebrohepatorenal) syndrome
âĸ Neonatal adrenoleukodystrophy
âĸ Infantile Refsum disease
âĸ Hyperlipopecolaternia
93. MITOCHONDRIA
Mitochondria have two membranes , They synthesize
adenosine triphosphate (ATP), contain their own doublestranded circular DNA, and make some of their own
proteins.
īĸ Mitochondria have several compartments :
Outer Membrane
īĸ The outer membrane is smooth, continuous, and
highly permeable.
īĸ It contains an abundance of porins, an integral
membrane protein that forms channels in the
outer membrane through which molecules of less
than 10 kD can pass.
īĸ
94. Inner Membrane
īĸ The inner membrane is inpermiable to most small ions (Na,
K*, H*) and small molecules (ATP, adenosine diphosphate,
pyruvate).
īĸ The impermeability is likely related to the high content of
the lipid cardiolipin.
īĸ The inner membrane has numerous infoldings, called
cristae.
īĸ The cristae greatly increase the total surface area. They
contain, enzymes for electron transport and oxidative
phosphorylation.
īĸ The number of mitochondria arid the number of cristae per
mitochondrion are proportional to the metabolic activity of
the cells in which they reside.
95.
96. Mitochondria
Two types of cristae: tubular-like and plate-like.
Most cells contain mitochondria with plate-like cristae. Steroid
secreting cells (eg. Adrenal, gonadal cells) have tubular cristae
98. Intermembrane Compartment :
īĸ The intermembrane compartment is the space between
the inner and outermembranes.
īĸ It contains enzymes that use ATP to phosphorylate other
nucleotides (creatine phosphokinase and adenylate kinase).
Matrix :
īĸ The matrix is enclosed by the inner membrane and
contains:
Dehydrogenases : oxidize many of the substrates in the
cell (pyruvate, amino acids, fatty acids), generating
reduced nicotinamide adenine dinucleotide (NADH) and
reduced flavin adenine dinucleotide (FADH,) for use by
the electron transport chain and energy generation.
100. A double-stranded circular DNA genomeâencodes a
few of the mitochondrial proteins.
īĸ Mitochondrial DNA is always inherited from the
mother, resulting in transmission of diseases of enery
metabolism.
īĸ RNA, proteins and ribosomesâalthough there is some
protein synthesis, most mitochondrial proteins are
synthesized in the cytoplasm and are transferred into the
mitochondria.
Intramitochondrial granule : contain calcium and
magnesium. Their function is not known, but it is
believed that they may represent a storage site for
Calcium.
īĸ
103. Cytoskeleton
Cells contain 3 categories of cytoskeletal elements
âĸMicrofilaments (actin filaments)
âĸIntermediate filaments
âĸMicrotubules
104. MICROTUBULES
īĸ
Small hollow cylindrical unbranched tubules 25 nm in
diameter with a 5nm thick wall.
īĸ
Made of 13 tubulin protofilaments arranged side by side
around a central core
105.
106. Microtubules play a role in:
Chromosomal movement during meiosis and mitosis.
īĸ Microtubule assembly is an important event in spindle
formation.
īĸ Intracellular vesicle and organelle transport. Two
specific microtubuledependent ATPases, kinesin and
dynein, are involved in generating the force that drives
transport, with the rnicrotubular structure playing a more
passive role in intracellular transport.
īĸ Ciliary and flagellar movement.
īĸ
107. The heterodimer, the subunit
of microtubule,is composed of
ι and β tubulin molecules.
īĸ
It is organized into a spiral
during polymerization.
īĸ
A total of 13 units are
present in one complete
turn of the spiral.
īĸ
109. âĸMicrotubule formation generally occurs more rapidly at
one end of existing microtubules.
âĸ This end is called the plus (+) end, and the other end as the
minus (-) end.
111. Kinesins:
Motor protein responsible for
moving vesicles and organelles
away from cell center.
Dyneins:
Responsible for movement
on microtubule towards the
cell center.
112. âĸMicrotubule formation directed by microtubule organizing
center.
âĸIs under control of concentration of Ca 2+ & microtubule
associated proteins (MAPs).
114. CHEDIAK - HIGASHI SYNDROME :
īĸ
Defect in microtubule polymerization .
īĸ
is an autosomal recessive immunodeficiency disorder
characterized by abnormal intracellular protein transport.
īĸ
Leads to delayed fusion of phagosomes with lysosomes
in leukocytes
115.
116.
117. Centrioles
A pair of cylindrical structures with
their long axis perpendicular to each
other.
Each is composed of 9 sets of
Microtubule triplets arranged in the
fashion of pinwheel.
119. Functions of centrioles
Non-dividing cells:
âĸPolymerization of long single microtubules that radiate throughout
the cytoplasm
âĸMaintain cell shape
âĸTransportation of substances
Dividing cells:
âĸForm mitotic spindles
121. Microfilaments
âĸMade up of polymers of the protein actin
âĸActin present as globular form (G-actin) & filamentous form
(F-actin).
âĸF-actin polymerizes forming helically entwined actin chains
âĸThese chains easily dissociate &reassemble with changes in
levels of Ca 2+ & cAMP change.
127. Intermediate filaments
âĸ
Vimentin : in cells of mesenchymal origin; may
contribute to position the nucleus in the cell; polymerize
with other intermediate filaments
âĸ
Desmin : Z-disks of skeletal muscle cells, where they
link actin filaments of adjacent sarcomeres, ensure
uniform tension distribution
âĸ
Glial fibrillary acid protein : characteristic of the
cytoplasm of glial cells (astrocytes)
âĸ
Neurofilaments : formed by three distinct proteins, they
are present in the cytoplasm of neurons
âĸ
Keratins : in cells of the skin for resistance to friction &
cell to cell adhesion
129. cell membrane
Apical cell membrane:
Regulation of nutrient and water intake
Regulated secretion
Protection
Lateral cell membrane:
Desmosomes or macula
adherens
Cell contact and adhesion
Cell communication
Basal cell membrane:
Cell substratum contact
Generation of ion gradients
Type IV collagen ,glycoproteins
133. Tight Junction (Zonula Occludens) :
īĸ
The tight junction is formed by the fusion of opposed
cell membranes. These ridges of fusion present as
"sealing strands" seen in freeze-fracture replicas.
īĸ
It extends completely around the apical cell borders to
seal the underlying intercellular clefts from contact with
the outside environment.
īĸ
It constitutes the anatomic component of many barriers
in the body.
134.
135. Zonula Adherens :
īĸ
A zonula adherens (adherent junction) often lies
basal to the zonula occludens.
īĸ
It is a bandlike junction that serves in the
attachment of adjacent epithelial cells.
137. Desmosome
īĸ The desmosome (macula adherens) is formed by the
juxtaposition of two disk-shaped plaques contained within the
cytoplasm of each adjacent cell
īĸ Intermediate filaments (tonofilaments) radiate away from the
plaques.
īĸ These intermediate filaments are anchored by desmoplakins
(plaques) that also bind to transmembrane linker proteins,
linking adjacent cells.
īĸ Cadherin molecules form actual anchor by attaching to
cytoplasmic plaque, extending through the membrane and
binding strongly to cadherins coming through the membrane
of adjacent cell.
īĸ Desmosomes are most common in lining membranes, are
subject to wear and tear, and are considered spot welds that
hold cells together.
139. Gap Junction :
īĸ The gap junction is an area of communication between
adjacent cells that allows the passage of very small
particles an ions across a small intercellular gap within
the junction .
īĸ The gap junction consists of a hexagonal lattice of
tubular protein subunits called connexons, which form
hydrophilic channels connecting the cytoplasm of
adjacent cells.
īĸ This permits the direct passage of ions and small
molecules between cells to conduct electrical impulses.
140. BASEMENT MEMBRANE
īĸ
The basement membrane is a sheet like structure that
underlies virtually all epithelia.
It consists of
īĸ Basal laminaâcomposed of type IV collagen,
glycoproteins (e.g.,laminin), and proteoglycans
(e.g., heparan sulfate).
īĸ Reticular laminaâcomposed of delicate reticular fibers.
141. Hemidesmsomes
Points of contact between cell and the extracellular matrix.
Intermediate filaments of the cytoskeleton are inserted into
disc shaped electron dense attachment plaque on the
inside of the cell membrane.
142. APICAL (FREE) SURFACE
SPECIALIZATIONS
Microvilli :
īĸ Microvilli are apical cell surface evaginations of cell
membranes that function to increase the cell surface area
available for absorption.
īĸ A thick glycocalyx coat covers them. The core of each
microvillus contains actin microfilaments.
īĸ It is anchored in the apical cell cytoplasm to the terminal
web, which itself is anchored to the zonula adherens of
the cell membrane.
143.
144. Cilia :
īĸ Cilia are apical cell surface projections of cell membrane
that contain microtubules
īĸ They are inserted on centriole-like basal bodies present
below the membrane surface at the apical pole.
īĸ Cilia contain two central microtubules surrounded by a
circle of nine peripheral microtubule doublets.
īĸ The peripheral doublets are fused so that they share a
common tubule wall and form two subtubules, A and B.
īĸ Adjacent doublets are connected to one another by nexin
links
148. Movement of Cilia :
īĸ A pair of Dynein arms is attached to each A subtubule.
The arms bind to ATP and rearrange themselves so that a
binding site for the B subtubule in the tip of the arm is
exposed.
īĸ The B tubule interacts with the binding site, causing the
arm to snap back and movement to occur.
īĸ Each cycle of a single dynein arm slides adjacent
doublets 10 nm past each other.
īĸ Cilia move back and forth to propel fluid and particles in
one direction.
īĸ They are important in clearing mucous from the
respiratory tract.
151. īĸ
Labile cells :
are dividing all the time--always in the cell cycle.
Examples : cells in the Digestive tract,
Skin,
Respiratory tract,
and Stem cells in the bone marrow
producing blood cells.
152. STABLE CELLS
īĸ
Also known as quiescent cells
īĸ
Normally they have a low level of
replication
īĸ
Can rapidly divide in response to
stimuli
īĸ
Cells that make up glandular organs
is an example of stable cells
pancreatic cells
During those periods of
high mitotic rate, they are
vulnerable to mutation &
consequent
malignancies
153. PERMANENT CELLS
īĸ
Unable to divide
īĸ
Can increase in size and
accelerate their function
īĸ
Examples:
Brain
Renal corpuscles
Cardiac muscle
cardiac muscle
Very resistant to neoplasia!
Editor's Notes
Membrane structure :
(a): A TEM of a sectioned cell surface shows the trilaminar unit membrane with two dark (electronâdense) lines enclosing a clear (electronâlucent) band.
These three layers of the unit membrane correspond to reduced osmium deposited on the hydrophilic phosphate groups present on each side of the internal bilayer of fatty acids where osmium is not deposited.
The âfuzzyâ material on the outer surface of the membrane represents the glycocalyx of oligosaccharides attached to phospholipids and proteins.
Components of the glycocalyx are important for cellâcell recognition in many biological processes and for adsorption and uptake of many molecules by cells.
(b): Schematic drawing depicts the trilaminar ultrastructure (left) and molecular organization (right) of the lipid bilayer in a cell membrane.
The shaded bands at left represent the two dense layers observed in the TEM caused by the deposit of osmium in the hydrophilic portions of the phospholipid molecules.
The right side of the diagram shows the orientation of the phospholipids that form the bilayer of biological membranes.
The hydrophilic polar heads of the phospholipids are directed toward each surface of the membrane, in direct contact with water, and the hydrophobic nonpolar fatty acid chains of the phospholipids are buried in the middle, away from water.
Cholesterol molecules are interspersed throughout the lipid bilayer, affecting the packing and fluidity of the fatty acid chains.
The fluid mosaic model of membrane structure :
(a): The fluid mosaic model emphasizes that a membrane consisting of a phospholipid bilayer also contains proteins inserted in it or bound to the cytoplasmic surface (peripheral proteins) and that many of these proteins move within the fluid lipid phase.
Integral proteins are firmly embedded in the lipid layers. Other proteins completely span the bilayer and are called transmembrane proteins.
Hydrophobic amino acids of the integral membrane protein interact with the hydrophobic fatty acid portions of the membrane.
Both the proteins and lipids may have externally exposed oligosaccharide chains.
When cells are frozen and fractured (cryofracture), the lipid bilayer of membranes is often cleaved along the hydrophobic center.
Membrane proteins :
plasma membrane structure shows a globular peripheral protein on the external face of the membrane and two integral transmembrane proteins.
Oneâpass transmembrane proteins have single hydrophobic regions along the length of amino acids and for maximal stability this becomes buried in the internal region of the lipid bilayer.
Multipass transmembrane proteins have several hydrophobic amino acid sequences all buried in the bilayer, with terminal and intervening hydrophilic sequences exposed at either the external or cytoplasmic face of the membrane.
Many physiologically important membrane proteins, including ion pumps and channels, are multipass proteins.
Formation and maturation of cell membrane proteins :
Membrane proteins of the plasmalemma are synthesized in the rough endoplasmic reticulum and then move in transport vesicles to a Golgi apparatus, another cytoplasmic structure with several flattened membrane saccules or cisternae.
While in the Golgi apparatus, the oligosaccharide chains are added (glycosylation) to many membrane proteins by enzymes in the Golgi saccules.
When glycosylation and other posttranslational modifications are complete, the mature membrane proteins are isolated within vesicles that leave the Golgi apparatus.
These vesicles move to the cell membrane and fuse with it, thus incorporating the new membrane proteins (along with the lipid bilayer of the vesicle) into the cell membrane.
Endocytosis and membrane trafficking :
Ligands, such as hormones and growth factors, are internalized by receptorâmediated endocytosis, which is mediated by the cytoplasmic peripheral membrane protein clathrin or other proteins which promote invagination and temporarily coat the newly formed vesicles.
Such coated vesicles can be identified by TEM.
After detachment of the coating molecules, the vesicle fuses with one or more vesicles of the endosomal compartment, where the ligands detach from their receptors and are sorted into other vesicles.
Vesicles of membrane with empty receptors return to the cell surface and after fusion the receptors are ready for reuse.
Vesicles containing the free ligands typically fuse with lysosomes, as discussed below.
The cytoskeleton with associated motor proteins is responsible for all such directional movements of vesicles.
Internalization of lowâdensity lipoproteins :
Endocytosis of lowâdensity lipoproteins (LDL) is an important mechanism that keeps the concentration of LDL in extracellular body fluids low and is a wellâstudied example of endocytosis and membrane trafficking. LDL, which is often rich in cholesterol, binds with high affinity to its specific receptors in the cell membranes.
This binding activates the formation of clathrinâcoated endocytotic pits that form coated vesicles.
The vesicles soon lose their coat proteins, which return to the inner surface of the plasmalemma.
The uncoated vesicles fuse with endosomes and the free LDL and the receptors are sorted into separate vesicles.
Receptors are returned to the cell surface and the LDL is transferred to lysosomes for digestion and separation of their components to be utilized by the cell.
G proteins and initiation of signal transduction :
When a hormone or other signal binds to a membrane receptor, the hormone can begin to cause changes in the cellâs activities after a signal transduction process initiated by the bound receptor.
The first step in receptor signaling often involves G proteins which bind guanosine diphosphate (GDP) when inactive and are activated when GDP is exchanged for GTP.
A simplified version of G protein activity is shown here.
Conformational changes occur in the receptor when it binds its ligand and the changed receptor activates the G proteinâGDP complex.
A GDPâGTP exchange releases the Îą subunit of the G protein, which then moves laterally to bind with a transmembrane effector protein, activating it to propagate the signal further by various mechanisms.
The Îą subunit GTP is rapidly converted back to GDP, allowing the polypeptide to reassociate with the rest of the G protein complex, ready to be activated again when the receptor is again bound by hormone.
Nuclei of large, active cells :
Liver cells (hepatocytes) have large, wellâstained nuclei located in the center of the cytoplasm.
One or more nucleoli are seen inside each nucleus, indicating intense protein synthesis by these cells.
Most of the chromatin is lightâstaining or euchromatic, with small areas of more darkly stained heterochromatin scattered throughout the nucleus and just inside the nuclear envelope.
This superficial heterochromatin allows the boundary of the organelle to be seen more easily by light microscopy.
One cell here has two nuclei, which is fairly common in the liver. Pararosanilineâ toluidine blue.
Nuclear pores :
TEM micrographs show nuclear envelopes and nuclear pores between nucleus (N) and cytoplasm (C).
(a): Section through the nuclear envelope and the twoâmembrane structure of the nuclear envelope clearly.
The electronâdense proteins that make up the nuclear pore complexes can also be seen (arrows).
Immediately beneath the nuclear envelope is the nuclear lamina and heterochromatin, material that is not present however at the nuclear pores.
(b): Tangential section through a nuclear envelope shows the electronâdense nuclear pore complexes (arrows) and the electronâlucent patches in the peripheral heterochromatin which represent the areas just inside the pores.
Nuclear pores :
TEM micrographs show nuclear envelopes and nuclear pores between nucleus (N) and cytoplasm (C).
(a): Section through the nuclear envelope and the twoâmembrane structure of the nuclear envelope clearly.
The electronâdense proteins that make up the nuclear pore complexes can also be seen (arrows).
Immediately beneath the nuclear envelope is the nuclear lamina and heterochromatin, material that is not present however at the nuclear pores.
(b): Tangential section through a nuclear envelope shows the electronâdense nuclear pore complexes (arrows) and the electronâlucent patches in the peripheral heterochromatin which represent the areas just inside the pores.
Cryofracture of nuclear envelop showing nuclear pores :
Electron micrograph obtained by freezeâfracture of an intestinal cell shows the two components of the nuclear envelope and the nuclear pores.
The fracture plane occurs partly between the two nuclear envelope membranes (left) but mostly just inside the envelope with the chromatin falling away.
The size and distribution of the nuclear pore complexes are clearly seen.
The same nuclear pore complexes can mediate both the import and export of macromolecules between the nucleus and cytoplasm using tightly controlled processes in each direction.
Relationship of nuclear envelope to the rough ER :
Threeâdimensional representation of a cell nucleus shows a single large nucleolus and the distribution of the nuclear pores in the envelope.
The number of nuclear pores varies greatly from cell to cell, increasing in cells actively involved in protein synthesis.
Structural components of the nucleus :
(a): TEM of a typical cell nucleus clearly shows the electronâdense heterochromatin (HC) and the more diffuse euchromatin (EC).
The arrows indicate the nucleolusâassociated heterochromatin around the nucleolus (NU).
Arrowheads indicate areas where the perinuclear space between the two membranes of the nuclear envelope is clearly seen.
Just inside the nuclear envelope is a thin electronâdense region containing the nuclear lamina and more heterochromatin. X26,000.
(b): Schematic representation of a cell nucleus shows that the nuclear envelope is made of two membranes separated by the perinuclear space.
The outer membrane has ribosomes bound to it and is continuous with the ER. The two membranes fuse at many places to form nuclear pores.
Heterochromatin clumps (HC) are associated with the meshwork of the nuclear lamina just inside the nuclear envelope, whereas the euchromatin (EC) appears dispersed in the interior of the nucleus.
The nucleolus contains distinct regions called the pars granulosa (G) and the pars fibrosa (F).
Nuclear lamina :
The nuclear lamina is formed from a class of intermediate filaments proteins, the lamins, which assemble as a lattice adjacent to the inner nuclear membrane.
When the nuclear envelope disperses during early prophase of cell division, at least some lamin proteins remain attached to the membrane fragments and reassembly of the nuclear lamina immediately after cell division facilitates reâformation of the nuclear envelopes of the two new nuclei.
The nuclear lamina also contains binding sites for chromatin, helping to organize this material in the nucleus.
Chromatin is not present at the openings through the nuclear envelope called nuclear pore complexes.
Nucleoli :
Primary oocytes are very large cells with very large round euchromatic nuclei.
The cells are actively increasing in volume, synthesizing much protein and many ribosomes, and each nucleus has one wellâdeveloped, intensely basophilic nucleolus.
The strong basophilia reflects the high concentration of rRNA being processes in this small region of nucleoplasm.
Other cells may each have one large nucleolus or a few smaller nucleoli.
All are involved in transcription and processing of rRNA.
Primary oocytes arrest for a prolonged period during prophase of the first meiotic division, when the chromosomes have already begun to condense.
Parts of the condensed chromosomes are seen as the stained material in the sectioned nuclei shown here.
Meiosis in oocytes will proceed just before they are ovulated (extruded from the ovary; see Chapter 22).
Components of a nucleosome :
Nucleosome is a structure that produces the initial organization of free doubleâstranded DNA into chromatin.
Each nucleosome has an octomeric core complex made up of four types of histones, two copies each of H2A, H2B, H3, and H4. Around this core is wound DNA approximately 150 base pairs in length.
One H1 histone is located outside the DNA on the surface of each nucleosome.
DNA associated with nucleosomes in vivo thus resembles a long string of beads.
Nucleosomes are very dynamic structures, with H1 loosening and DNA unwrapping at least once every second to allow other proteins, including transcription factors and enzymes, access to the DNA.
Structural components of the nucleus :
(a): TEM of a typical cell nucleus clearly shows the electronâdense heterochromatin (HC) and the more diffuse euchromatin (EC).
The arrows indicate the nucleolusâassociated heterochromatin around the nucleolus (NU).
Arrowheads indicate areas where the perinuclear space between the two membranes of the nuclear envelope is clearly seen.
Just inside the nuclear envelope is a thin electronâdense region containing the nuclear lamina and more heterochromatin. X26,000.
(b): Schematic representation of a cell nucleus shows that the nuclear envelope is made of two membranes separated by the perinuclear space.
The outer membrane has ribosomes bound to it and is continuous with the ER.
The two membranes fuse at many places to form nuclear pores.
Heterochromatin clumps (HC) are associated with the meshwork of the nuclear lamina just inside the nuclear envelope, whereas the euchromatin (EC) appears dispersed in the interior of the nucleus.
The nucleolus contains distinct regions called the pars granulosa (G) and the pars fibrosa (F).
Golgi apparatus :
Though only snapshots of this highly dynamic organelle, electron micrographs of the Golgi apparatus provided early evidence about how this organelle functions, evidence that has now been strengthened by biochemical and other studies.
To the right is a cisterna (arrow) of the rough ER containing granular material.
Close to it are small vesicles containing apparently similar material.
These are very close to the cis face of the Golgi apparatus.
In the center are the characteristic flattened, curved, and stacked medial cisternae of the complex.
Dilatations (upper left arrow) are seen extending from the ends of the cisternae.
Similar dilatations gradually detach themselves from the cisternae and fuse at the trans face, forming the secretory granules
Summary of Golgi apparatus structure and function :
Summary of the main events occurring during protein trafficking and sorting from the rough ER through the Golgi complex. Numbered at the left are the main molecular processes that take place in the compartments shown.
In the trans Golgi network, the proteins and glycoproteins combine with specific receptors that guide them to the next stages toward their destinations.
On the left side of the drawing is the returning flux of membrane, from the Golgi to the endoplasmic reticulum.
liver, the proximal tubules of the kidney, and endocrine glands