Receptors and Signalling I Flashcards
Why is knowing how cell signalling occurs helpful?
Helps to eliminate disease especially when that disease causes problems with cell signalling
All cells have receptors or signalling mechanisms
Why is cell signalling so important within the body?
Survival is dependent upon a cells ability to sense and react to its environment
What is homeostasis and how is it achieved?
Equilibrium between the interdependent systems of the body in a multicellular organsim requiring a cell to communicate with its environment and between other cells
What do we need to convey information?
Receptor (extracellular or intracellular) and ligands that bind to the receptors
What types of signalling are there?
- Contact-dependent (cell-cell communication cell with receptor and cell with transmembrane signal)
- Paracrine (ligand released to neighbouring cells)
- Synaptic (nerves transfering information via action potentials) more enrgy intensive
- Endocrine (target cell far away from ligand producer)
- Autocrine (target cell is the ligand producing cell) cell acts on itself
What are hormones?
Broad group of factors released by cells of one tissue, carried to new site of action (endocrine etc.) e.g.
Small water soluble molecules (adrenaline)
Peptide hormones (insulin)
Lipophilic molecules (prostaglandins)
What are growth factors?
Signalling molecule that regulate growth and differentiation of cells
What are cytokines?
Peptide molecules that have local effects (paracrine) e.g. interleukins
May be delivered in solution or be attached to an adjacent cell or is an ECM constituent
What are examples of intracellular signals?
- Gases such as nitric oxide diffuse across cell membranes readily and cause a direct effect
- Steroids binding to specific receptors within the cell, activating the receptor which becomes a transactivator regulating gene expression
Give the names of the 3 major classes of cell surface receptors
- G-protein couple receptors (GPCRS)
- Ion channel linked receptoes
- Enzyme linked receptors
How do Ion channel linked receptors transduce a signal?
Receptors span the plaasma membrane of the cell, when the specific ligand binds a conformational change occurs that allows ions at high concentration on one side of the membrane to move to a lower concentration on the other side of the membrane thorugh the pore.
Very quick process that usually work with neurotransmitters such as Acetylcholine
denyHow do GPCRs transduce a signal?
The receptor (7-pass transmembrane protein) is linked to a G (guanyl) protein, when the ligand binds the G protein is activated, G protein the activates effector such as an enzyme to produce a response such as adenylyl cyclase activity for increased cAMP production
How is diversity of GPCRs achieved?
G protein made up of 3 subunits (alpha, beta, gamma)
Alpha subunit usually defines the G-protein with 20 different isoforms however beta and gamma subunits also have isoforms
Explain second messenger cAMP in regards to GPCRs
Stimulatory G-proteins signal using secondary messenger cAMP e.g. The activated G-protein interacts with the enzyme adenylyl cyclase at the membrane which generates cAMP from ATP, producing a rapid rise in cAMP concentration.
cAMP the activates cAMP-sependent protein kinase which phosphorylates protein substrates to affect cells
How is the signal deactivated (GPCRs)?
- Alpha subunit has intrinsic GTPase activity which convertys the bound GTP to GDP reuniting the alpha subunit with the beta and gamma subuits inactivating the G-protein
- cAMP rapidly destroyed by PDE (cAMP > AMP)
- Serine/threonine phosphotases dephosphorylate proteins that were phosphorylated via PKA
- Receptor becomes desensitised to further stimulation via phosphorylation of the receptor leading to the receptor being internalised by receptor-mediated endocytosis and the receptor being uncoupled from its g-protein
- Also the ligand is destroyed as a result of receptor-mediated endocytosis
