SCMOL3001 Lecture 3: Cellular Signalling Systems

These flashcards cover key concepts from the lecture on cellular signaling systems, focusing on GPCRs, their activation, second messengers, and associated pathways.

What are G‐protein coupled receptors (GPCRs)?

The largest family of cell‐surface receptors that transduce signals from the external environment and other cells.

They use a complex of G-proteins to relay signals.

Describe the structure of G-protein coupled receptors

GPCRs are transmembrane proteins, consisting of seven alpha-helices, in a barrel like complex, that span the cell membrane and interact with G-proteins on the intracellular side. The ligand binding site is at the center of the “barrel”.

Describe the function of G-protein coupled receptors

GPCRs transduce signals across the lipid bilayer via the second messenger effect.

GPCR becomes activated by binding a ligand, and then membrane bound G-protein complexes become associated with the GPCRs cytoplasmic region

The are four broad groups of GPCRs, grouped based on the similarities of the alpha subunit amino acid sequence, and therefor the action of the alpha and beta/gamma subunits.

Some functions of each family:

Family 1 - can activate adenylyl cyclase, and calcium channels.

Family 2 - can inhibit adenylyl cyclase, and calcium channels. can activate potasium channels. can activate phospholipase C-beta.

Family 3 - can activate phospholipase C-beta.

Family 4 - can activate Rho family monomeric GTpases, via Rho-GEF, to regulate the actin cytoskeleton.

What is a G-protein? Describe the structure and function.

A complex of 3 subunits; alpha, beta, and gamma. The alpha and gamma are membrane bound, and the beta is bound to the gamma.

The G-protein can switch between an active and inactive state. When inactive, G-alpha carries GDP, LICC in the GPCR causes it to behave like a GEF and activate the G-protein: GDP is exchanged for GTP and the protein undergoes a conformational change. The change causes the G-alpha protein to dissociate from the G-beta/gamma pair, and release from the receptor. The G-alpha, and the G-beta/gamma, regulate downstream signalling molecules.

G-alpha has intrinsic GTPase action, and can become inactive again by hydrolysing it’s bounf GTP to GDP.

This hydrolysis can be modulated by the target protein or a specific RGS - regulator of G-protein signalling.

After all GTP has been hydrolysed to GDP, G-proteins reassemble into their original tri protein complex.

How does a GPCR become activated?

A ligand binds to the receptor, inducing a conformational change that activates the associated G-protein.

What happens during G-protein activation?

Gα exchanges GDP for GTP, resulting in the dissociation of GαGTP from Gβγ.

What role do Cholera and Pertussis Toxins play in G-protein signaling?

Cholera toxin prevents GTP hydrolysis, keeping the effector active, while Pertussis toxin prevents the reassociation of the Gi protein.

What is the function of adenylyl cyclase (AC) in the cAMP signaling pathway?

AC converts ATP to cyclic AMP (cAMP), a second messenger, upon activation by GαGTP.

What is the role of calcium ions in cellular signaling?

Calcium ions serve as a secondary messenger that can trigger various intracellular responses when released from the ER.

What is calmodulin and what is its function?

Calmodulin is a calcium-binding protein that, upon binding Ca2+, activates calcium-dependent kinases like CaM kinase.

What is the Ras pathway and its significance?

The Ras pathway involves Ras activation by receptor tyrosine kinases, promoting cell proliferation through MAP kinase signaling.

How does DAG (diacylglycerol) function in cellular signaling?

DAG activates protein kinase C (PKC), which phosphorylates serine and threonine residues on target proteins.