physiology

1. Signal Transduction

2. Signal Transduction
(Old terms:Signal transmission or sensory transduction)
In this phenomenon a mechanical or chemical
stimulus is converted into a specific cellular
response. It starts with a signal to a receptor,
and ends with a change in cell function or
response.

3. Signal Transduction
• Cells respond to their environment by re-
organizing their structure, regulating the activity
of proteins and altering patterns of gene
expression.
• The stimulus for such responses is known as
signal.
• It may be a small molecule, a macromolecule or
a physical agent such as light, temperature,
water etc.

4. • Signals interact with the responding cell through
specific molecules called receptors.
• Small molecules often act as diffusible signals.
In unicellular organizations diffusible signals
may be environmental or may be released from
other cells e.g. yeast mating-type pheromones .
• Molecular signal that binds to a receptor is
called ligand.

5. Signal Transduction in Prokaryotes
• Animal (mammals) possess a well developed
nervous system by which they are able to sense
and respond to environment.
• Many processes such as
• Stimulus detection
• Signal amplification
• Appropriate output responses are present in all
cell sensory systems including bacteria.
• Many bacterial signaling pathways consist of
molecular units called transmitters and
receivers. This is called two-component
regulatory system.

6. • Bacteria use two component regulatory systems
to sense extracellular signals. They sense
chemicals in the environment by means of a
small family of cell surface receptors, each
involved in the response to a specific group of
chemicals called ligands.
• A protein in the plasma membrane of bacteria
binds directly to a ligand or binds to a soluble
protein that has already attached to the ligand,
in the periplasmic space between the PM and
the cell wall.
.

7. • Upon binding, the membrane protein undergoes
a conformationational change that passes
across the membrane to the cytosolic domain of
the receptor protein. This conformational change
initiates the signaling pathway that leads to the
response.

8. Signaling via bacterial two-component-
systems
• The sensor protein present on cell wall detects
the stimulus via the input domain and transfers
the signal to the transmitter domain by means of
conformational change (first dashed arrows).
• The transmitter domain of the sensor then
communicates with the response regulator by
protein phosphorylation of the receiver domain.

9. • Phosphorylation of the receiver domain induces
a conformational change (second dashed
arrows) that activates the output domain and
brings about the cellular response.
• For instance, osmoregulation, chemotaxis and
sporulation are regulated by two component
system.

11. • The signal is passed from transmitter domain to
receiver domain due to protein phosphorylation.
• Transmitter domains have the ability to
phosphorylate themselves using ATP on a
histidine near the amino terminus. Because of
this autophosphorylation, the sensor proteins
containing transmitter domains are called
autophosphorylating histidine kinases.

12. Hormones
• There are two classes of hormones depending
on their ability to move across the plasma
membrane.
– Lipophilic hormones: which diffuse readily
across the hydrophobic bilayer of plasma
membrane e.g. Androgens, glucocorticoids,
estrogens and brassinosteroids.
– Water soluble hormones which are unable
to enter the cell by their own e.g. antidiuretic
hormone (ADH), glucagons, Thyroid
Stimulating Hormone (TSH)

13. • Lipophilic hormones bind mainly to receptors in
the cytoplasm or nucleus, whereas water soluble
hormones bind to receptors located on the cell
surface.
• In both cases ligand binding changes the
receptor by causing a conformational change.
• Some receptors such as steroid hormone
receptors can regulate gene expression directly.

14. • But in most cases the receptor initiates one or
most sequences of biochemical reactions that
connect the stimulus to a cellular response.
Such a sequence of reactions is called a signal
transduction pathway.
• The final or end result of signal transduction
pathways is to regulate transcription factors
which in turn regulate gene expression.

15. Signal transduction pathway
• Signal transduction pathways often involve
generation of second messengers. They actually
transmit secondary signals inside the cell that
greatly amplify the original signal.
• Molecules inside the cells that act to transmit
signals from a receptor to a target. The term
second messenger is used to distinguish them from
hormones and other molecules that function
outside the cell as “first messengers” in the
transmission of biological information.

16. • Most common second messengers are cAMP,
cGMP, 1,2 diacylglycerol (DAG), or inositol 1,4,5
triphosphate or inositol 4,5,6 triphosphate (IP3)
and Ca2+.
• Hormones binding normally causes enhanced
levels of one or more of these second
messengers resulting in the activation or
inactivation of enzymes or regulatory proteins.