Animal biotechnology

1. Cell Signaling(signaling through G-
protien coupled receptors,signal
transduction pathways
Senthurapandi M
ll M.sc Biotechnology
Allagapa University

4. Introduction
• Cell signaling is part of any communication process
that governs basic activities of cells and coordinates all
cell actions.
• The ability of cells to perceive and correctly respond to
their microenvironment is the basis of development,
tissue repair, and immunity as well as normal tissue
homeostasis.
• Errors in signaling interactions and cellular information
processing are responsible for diseases like???????
• By understanding cell signaling, diseases may be
treated more effectively and, theoretically, artificial
tissues may be created.[

5. Important words to know ……….
• RECEPTOR-a region of tissue, or a molecule in
a cell membrane, which responds specifically
to a particular neurotransmitter, hormone,
antigen, or other substance.
• Ligand-is usually a molecule which produces a
signal by binding to a site on a target protein.

6. Overview of cell signalling

7. Signaling
Transmission of a signal from a sending cell to a
receiving cell.
Not all sending and receiving cells are next-door
neighbors,
Nor do all cell pairs exchange signals in the same
way.

8. Four basic categories of chemical
signaling in Mo
• Paracrine signaling
• Autocrine signaling
• Endocrine signaling
• Signaling by direct contact.
• Difference between the different categories
of signaling is the distance that the signal
travels

9. Paracrine signaling
• Cells that are near one another communicate
through the release of chemical messengers
• cells communicate over relatively short
distances
• Important during development, when they
allow one group of cells to tell a neighboring
group of cells what cellular identity to take on.
[Example: spinal cord development and
synaptic signalling]

11. Synaptic signalling
• This process is named for the synapse, the
junction between two nerve cells where signal
transmission occurs

12. Autocrine signaling
• cell signals to itself, releasing a ligand that
binds to receptors on its own surface

13. Endocrine signaling
• Transmit signals over long distances, they often use
the circulatory system as a distribution network for
the messages they send
• Signals that are produced in one part of the body and
travel through the circulation to reach far-away
targets are known as hormones.

14. Signaling through cell-cell contact
• Gap junctions ?????????????
• plasmodesmata???????????
• Intracellular mediators

15. These water-filled channels allow small signaling
molecules, called intracellular mediators, to
diffuse between the two cells.

16. G-protein-coupled receptors (GPCRs)
• G-protein-coupled receptors (GPCRs) are the largest and
most diverse group of membrane receptors in eukaryotes.
• These cell surface receptors act like an inbox for messages
in the form of light energy, peptides, lipids, sugars, and
proteins.
• G protein–linked receptors (GPLR), constitute a large
protein family of receptors, that detect molecules outside
the cell and activate internal signal transduction pathways
and, ultimately, cellular responses.
• Coupling with G proteins, they are called seven-
transmembrane receptors because they pass through the
cell membrane seven times.[2]

17. History
• In 2012 Nobel Prize in Chemistry was awarded
to Brian Kobilka and Robert Lefkowitz for their
work that was "crucial for understanding how
G protein–coupled receptors function".

18. G Protein-Coupled Receptors
G protein-coupled receptors (GPCRs), also
known seven-transmembrane domain receptors
7TM receptors
serpentine receptor
G protein-linked receptors (GPLR)
They are called seven-
transmembrane receptors because they pass
through the cell membrane seven times

20. The ligands that bind and activate these receptors
include:
Light sensitive compounds
Hormones and
Neurotransmitters
That vary in size from small
molecules to peptides to large proteins.

21. Families of GPCR
3 Families:
A – Rhodopsin family
B - Secretin/Glucagon receptor family
eg. Peptide hormones.
C - Metabotropic Glutamate family
eg. GABAB , Glutamate.

22. Rhodopsin Receptor Family
RR are a family of proteins comprise
of G protein-coupled receptors and are extremely
sensitive to light.
Activates the G protein transducin (Gt) to activate
the visual phototransduction pathway.
Remaining receptors are liganded by
known Endogenous compounds.
Eg, receptor (FXR) farnesoid X receptor, which is
activated by bile acid,

23. Secretin Receptor Family
SR family of GPCRs include Vasoactive
intestinal peptide receptors
And receptors for
secretin
calcitonin
parathyroid hormone/parathyroid
hormone-related peptides.
These receptors activate adenylyl
cyclase and the phosphatidyl-inositol-calcium
pathway

24. Metabotropic Glutamate Family
MGluRs are family C GPCR that participate in
the modulation of synaptic transmission and
neuronal excitability throughout the central
nervous system.
MGluRS subdivided into three
groups, based on intracellular signalling
mechanisms.

25. Group 1
Group II
Group III receptors
are negatively coupled to adenylyl cyclase.
They widely distributed throughout
the mammalian brain with high levels in the
cerebellum and thalamus.

26. Structure of G Protein
G proteins, also known as guanine
nucleotide-binding proteins, involved in
transmitting signals and function as molecular
switches.
Their activity is regulated by factors
that control their ability to bind to and
hydrolyze guanosine triphosphate (GTP)
to guanosine diphosphate (GDP).
When they bind GTP, they are 'on', and,
when they bind GDP, they are 'off

27. G protein complexes are
Made up of alpha (α), beta (β)
and gamma (γ) subunits.
Beta and gamma subunits
can form a stable dimeric
complex referred to as the
beta-gamma complex

28. • G proteins located within the cell are activated
by GPCRs .
• Inside the cell, on the plasma membrane
G Protein binds GDP when inactive and GTP
when active.
GPCRs binds to a signal molecule
Receptor is activated and changes shape, thereby
allowing it to bind to an inactive G Protein.
When this occurs, GTP displaces GDP which activates
the G Protein

29. Newly activated G Protein migrates along the cell
membrane until it binds to adenylyl cyclase
which convert ATP to cAMP
leads to the next step in the pathway and
generates a cellular response.

31. Signal Transduction
conversion of a signal from outside the cell to a
functional change within the cell.
A signal (such as a hormone or neurotransmitter)
interacts with a receptor on the cell surface
Interaction causes a change in a second messenger (such
calcium)
Eventually, a change is triggered in the cell's function (for
example, the cell divides

33. Calcium based signal
transduction

35. Role of second messengers in signal
transduction pathway
• Secondary messengers are therefore one of
the initiating components of intracellular
signal transduction cascades.
Eg of second messenger molecules
include cyclic AMP, cyclic GMP, inositol
trisphosphate, diacylglycerol, and calcium.