cell cell interaction

1. Cell Biology
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Cell-to-Cell Communication
 Signaling molecules are secreted by cells and function in cell-to-cell communication.
Examples include neurotransmitters, which are released into the synaptic cleft endocrine
hormones, which are carried in the bloodstream and act on distant target cells; and hormones
released into the intercellular space, which act on nearby cells (paracrine hormones) or on the
releasing cell (autocrine hormones).
o Lipid-soluble signaling molecules penetrate the plasma membrane and bind to
receptors in the cytoplasm or nucleus, activating intracellular messengers. Examples
include hormones that influence gene transcription.
o Hydrophilic signaling molecules bind to and activate cell-surface receptors (as do
some lipid-soluble signaling molecules) and have diverse physiologic effects. Examples
include neurotransmitters and numerous hormones (e.g., serotonin, thyroid-stimulating
hormone, insulin).
 Membrane receptors are primarily glycoproteins. They are located on the cell surface,
and specific signaling molecules bind to them.
Function
o Membrane receptors control plasmalemma permeability by regulating the conformation
of ion channel proteins.
o They regulate the entry of molecules into the cell (e.g., the delivery of cholesterol via
low-density lipoprotein receptors).
o They bind extracellular matrix molecules to the cytoskeleton via integrins, which are
essential for cell-cell contact and cell-matrix interactions.
o They act as transducers to transfer extracellular events intracellularly to second
messenger systems.
o They permit pathogens that mimic normal ligands to enter cells.
Types of membrane receptors
o Channel-linked receptors bind a signaling molecule that temporarily opens or closes
the gate, permitting or inhibiting the movement of ions across the cell membrane.
Examples include nicotinic acetylcholine receptors on the muscle-cell sarcolemma at
the myoneural junction.
o Catalytic receptors are single-pass transmembrane proteins.
 Their extracellular moiety is a receptor, and their cytoplasmic aspect is a protein
kinase.
 Some catalytic receptors lack an extracytoplasmic moiety and as a result are
continuously activated; such defective receptors are coded for by some oncogenes.
 Examples of catalytic receptors include:
 Insulin, which binds to its receptor, which autophosphorylates. The cell then
takes up the insulin-receptor complex by endocytosis, enabling the complex to
function within the cell.
 Growth factors (e.g., epidermal growth factor, platelet-derived growth factor),
which bind to some catalytic receptors and induce mitosis.

2. Cell Biology
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 G-protein-linked receptors are transmembrane proteins associated with an ion
channel or with an enzyme bound to the cytoplasmic surface of the cell membrane.
 These receptors interact with heterotrimeric G-protein • [guanosine triphosphate (GTP)-
binding regulatory protein] after binding of a signaling molecule. This interaction results
in the activation of intracellular second messengers, the most common of which are
cyclic adenosine monophosphate (cAMP) and Ca2+.
 Examples include:
 Heterotrimeric G proteins , which include stimulatory G protein (Ge) , inhibitory G
protein (GO,phospholipase C activator G protein (Ge), olfactory-specific G protein
(Gold, and transducin (Gt)
 Monomeric G proteins (low-molecular-weight G proteins), which are small
single-chain proteins that also function in signal transduction
o Various subtypes resemble Ras, Rho, Rab, and ARF proteins.
o These proteins are involved in pathways that regulate cell proliferation and
differentiation, protein synthesis, attachment of cells to the extracellular matrix,
exocytosis, and vesicular traffic.
 Plasmalemma-Cytoskeleton Association.
 The plasmalemma and cytoskeleton associate through integrins. The extracellular
domain of integrins binds to extracellular matrix components, and the intracellular
domain binds to cytoskeletal components. Integrins stabilize the plasmalemma and
determine and maintain cell shape.

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 Red blood cells have integrins, called band 3 proteins, which are located in the
plasmalemma. The cytoskeleton of a red blood cell consists mainly of spectrin, actin,
band 4.1 protein, and ankyrin.
o Spectrin is a long, flexible protein (about 110 nm long), composed of an a-chain
and a 13-chain, that forms tetramers and provides a scaffold for structural
reinforcement.
o Actin attaches to binding sites on the spectrin tetramers and holds them together,
thus aiding in the formation of a spectrin latticework.
o Band 4.1 protein binds to and stabilizes spectrin-actin complexes.
o Ankyrin is linked to both band 3 proteins and spectrin tetramers, thus attaching
the spectrin-actin complex to transmembrane proteins.
 The cytoskeleton of nonerythroid cells consists of the following major components:
o Actin (and perhaps fodrin), which serves as a nonerythroid spectrin
o a-Actinin, which cross-links actin filaments to form a meshwork
o Vinculin, which binds to a-actinin and to another protein, called talin, which in
turn attaches to the integrin in the plasma membrane

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 Clinical Considerations
 Cystinuria is a hereditary condition caused by abnormal carrier proteins that are unable
to remove cystine from the urine, resulting in the formation of kidney stones.
 Cholera toxin is an exotoxin produced by the bacterium Vibrio cholerae.
o The cholera toxin alters G8 protein so that it is unable to hydrolyze its GTP
molecule.
o As a result, cAMP levels increase in the surface absorptive cells of the intestine,
leading to excessive loss of electrolytes and water and severe diarrhea.
 Venoms, such as those of some poisonous snakes, inactivate acetylcholine receptors of
skeletal muscle sarcolemma at neuromuscular junctions.
 Autoimmune diseases may lead to the production of antibodies that specifically bind to
and activate certain plasma membrane receptors. An example is Graves disease
(hyperthyroidism)
 Genetic defects
o Defective Gs proteins may lead to mental retardation, diminished growth and
sexual development, and decreased responses to certain hormones.
o Hereditary spherocytosis results from a defective spectrin that has a decreased
ability to bind to band 4.1 protein. The disease is characterized by fragile,
misshapen red blood cells, or spherocytes; destruction of these spherocytes in the
spleen leads to anemia.