Intracellular Signalling Flashcards
What is signal transduction?
A set of chemical reactions in a cell that occurs when a molecule, such as a hormone, attaches to a receptor on the cell membrane.
What is an agonist?
They bind to the receptor and activate it
What is an antagonist?
They bind to the receptor but do not activate it (block the effect of agonists)
Describe the basic structure of G-protein couples receptors:
Single polypeptide chain, 300-1200aa
7 transmembrane spanning regions
Extracellular N-terminal
Intracellular C-terminal
Where can a ligand bind to a GPCR?
The second and third transmembrane domain of the GPCR
The N-terminal
Summarise the ligand binding to GPCRs and the effect:
Ligand binding leads to conformational change, switching the receptor on. It then interacts with a G protein. The G protein changes it’s activity, it releases GDP. It binds with GTP.
How does the GPCR activate the G protein?
By causing the GDP to be exchanged for GTP on the alpha subunit of the G protein.
How is G protein signalling terminated?
The alpha subunit GTPase activity hydrolyses GTP to GDP and the two subunits form the inactive heterotrimeric complex
How does cyclic AMP dependant protein kinase exert actions?
It’s two catalytic subunits phosphorylate target proteins in the cell
(Has two regulatory units also)
How are increases in cytoplasmic Ca mediated?
Movement of Ca across the plasma membrane
Release of Ca from the ER/SR
How are increases in cytoplasmic Ca opposed?
Relative impermeability of the plasma membrane
Pumps and transporters that move Ca out
Ca buffer proteins (Ca binding proteins)
Mechanisms to reverse increases in [Ca]:
PMCA
SERCA
NCX
Mechanisms to increase [Ca]:
Across the PM:
Voltage operated Ca channels
Ligand gates ion channels
Out of ER/SR:
CICR/ryanodine receptors
Ionositol 1,4,5-trisphosphate receptors (IP3R)
How is IP3 made?
Phospholipase C catalyses the cleavage of the membrane phospholipid PIP2 into IP3 and DAG (second messengers).
Why is signal amplification important?
A few molecules of ligand can bring about a massive cellular response
