Intracellular signalling Flashcards
lecture 13
What is signal transduction?
The process by which an extracellular signal activates a membrane receptor, which then alters intracellular molecules, activating a cellular response
What happens during signal transduction?
One form of signal is converted into another
Why are signal transduction pathways important?
They allow communication between cells of different tissues or organs.
What are the first and second messengers in signal transduction?
The first messenger is the extracellular signal molecule, while intracellular molecules form the second messenger system.
Name 4 examples of extracellular signalling molecules.
Amines (e.g., adrenaline)
Peptides/proteins (e.g, insulin)
Steroids (e.g., hormones)
Other small molecules (e.g, amino acids, gases)
How do small non-polar molecules like steroids signal?
They diffuse through the plasma membrane and bind to intracellular receptors, often acting as transcription factors for gene regulation (slow response).
How do large polar molecules signal?
They bind to cell surface receptors, activating intracellular pathways for a faster response.
What are the 4 main classes of receptors?
- Ligand-gated ion channels
- G-protein coupled receptors (GPCRs)
- Enzyme-linked receptors
- Nuclear receptors
What are ionotropic receptors?
Receptors that form an ion channel pore, such as nicotinic acetylcholine and GABA 𝐴 receptors
What are metabotropic receptors?
Receptors indirectly linked to ion channels through G protein-mediated signal transduction pathways, such as muscarinic acetylcholine and GABA 𝐵 receptors.
Compare ionotropic and metabotropic receptors.
Ionotropic receptors directly open ion channels, while metabotropic receptors activate signalling pathways to affect channels indirectly.
What are the components of GPCRs?
3 subunits:
alpha (α),
beta (β),
gamma (γ).
What is the common structure of GPCRs?
7 transmembrane domains encoded by over 800 genes.
What happens in the G protein cycle when adrenaline binds to a β-adrenoreceptor?
The receptor activates G protein interaction, GDP is exchanged for GTP, the α subunit activates adenylyl cyclase, and a cellular response occurs
How does cAMP activate Protein Kinase A (PKA)?
cAMP binds to PKA’s regulatory subunits, releasing the catalytic subunits to phosphorylate target proteins.
Give examples of cellular responses mediated by the cAMP/PKA pathway.
Kidney: Water retention by vasopressin
Cardiac muscle: Increased heart rate by adrenaline
Pancreas: Glucose release by glucagon
How is signal transduction terminated?
Through signal or receptor removal/inactivation, dephosphorylation of proteins, or degradation of second messengers.
What is the role of phosphodiesterase in signal termination?
PDE hydrolyses cAMP, rapidly decreasing its concentration to turn off the response.
What happens during β-adrenoreceptor desensitisation?
Phosphorylation by β-ARK reduces receptor affinity for adrenaline, decreasing cellular response.
Describe the structure of inactive PKA.
A tetramer with regulatory (R) and catalytic (C) subunits bound together, suppressing catalytic activity.
How is PKA activated?
cAMP binding to R subunits releases active C subunits.
What does active PKA do?
Phosphorylates serine/threonine residues on substrate proteins, affecting cellular functions.
What does the nicotinic acetylcholine receptor do?
it forms an ion channel, allowing Na+ and Ca2+ entry upon acetylcholine binding, triggering electrical responses.
What does the GABA 𝐴 receptor regulate?
It allows Cl- ion entry, serving as an inhibitory receptor important in the CNS.
What does the muscarinic acetylcholine receptor regulate?
It activates signal transduction pathways via G proteins to affect ion channels indirectly.
What is the role of protein phosphorylation in signalling?
Kinases transfer phosphate groups to proteins, altering their activity and triggering cellular responses.
What is dephosphorylation, and what enzyme performs it?
Removal of phosphate groups by protein phosphatases, often deactivating the protein.
How does caffeine affect signal termination?
Caffeine inhibits PDE, prolonging cAMP levels and cellular responses.
Name a physiological response mediated by adrenaline through GPCRs.
Increased heart rate and relaxation of vascular smooth muscle.
What is the role of CREB in the cAMP pathway?
Phosphorylated by PKA, CREb activates the transcription of target genes.
What are the 3 main stages of signal transduction?
- Signal molecule binds receptor.
- Intracellular molecules relay the signal.
- Cellular response is activated.
