Lipids, Cell membranes and Signal transduction Flashcards
What are the 6 steps of cell-cell communication
- Synthesis of signal
- Release of the signalling molecule by the signalling cell: exocytosis, diffusion, cell-cell contact
- Transport of the signal to the target cell
- Detection of the signal by a specific receptor protein
- A change in cellular metabolism, function or development triggered by the receptor-signal complex
- Removal of the signal or desensitisation
What is endocrine signalling?
- An example of long range signalling
- Hormone released by endocrine cell and carried in bloodstream to distal target cells
What is an example of endocrine signalling?
Follicle-stimulating hormone released from the pituitary acts upon the ovary
What is an example of neurotransmission?
Breathing - the phrenic and thoracic nerves send impulses from the brain to the diaphragm
What is paracrine signalling?
- An example of short range signalling
- Signalling molecules only affect target cells in close proximity to secreting cells
What is an example of paracrine signalling?
Somatostatin release by pancreas cells acts locally
What is autocrine signalling?
Cells respond to substances that they themselves release
What is an example of autocrine signalling?
Some neurotransmitters and growth factors bind to the cells that release them
What is an example of membrane-bound proteins interacting to signal?
Signalling by T cells in the immune system
What is an example of membrane-bound proteins interacting to signal?
Signalling by T cells in the immune system
What are the two types of cell receptors?
- Cell-surface receptors (hydrophilic signal molecule)
- Intracellular receptors (hydrophobic signal molecule)
In more detail what are the four receptor types?
- Ligand-gated ion channels (ionotropic receptors)
- G-protein-coupled receptors (metabotropic)
- Kinase-linked receptors
- Nuclear receptors
Examples of lipid soluble molecules
- Steroid hormones
- Thyroxine
Examples of lipid soluble molecules
- Steroid hormones
- Thyroxine
Explain the inositol phospholipid signalling pathway
- Phosphatidylinositol 4,5-bisphosphate (PIP2) is a phospholipid found in the lipid bilayer
- It is the substrate of the enzyme phospholipase C (PLC)
- PLC liberates two signalling molecules from PIP2; inositol 1,4,5 triphosphate (IP3) and diacylglycerol (DAG)
How is calcium involved in cell signalling?
- Calcium concentration transiently increases in the cell in response to IP3 release
- Calcium binds to proteins to regulate their function
What is an example of calcium being used in signalling?
Ca2+/calmodulin - activates proteins/enzymes through direct interaction such as myosin light chain kinase
How is protein kinase C (PKC) involved in signalling?
- Calcium binds to C2 domain of PKC
- This allows C2 to interact with the plasma membrane
- This causes C1 domain to recognise and bind to the diacylglycerol that has been released
- This invokes a change in structure that causes the inhibitory domain of PKC to come away from the active sight activating the PKC and enabling it to phosphorylate and change the substrate molecules
What are some examples of PKC substrates?
- Tumour suppressor p53 (transcription factor) - prevents tumour formation
- Cav 1.2 (calcium channel) - heart muscle contraction
- IKKalpha (cytokine) - B cell activation (immune function)
What are eicosanoids (prostanoids)?
- Inflammatory mediators
- Considered local hormones
- Have specific effects on target cells close to their site of formation (autocrine/paracrine)
- Rapidly degraded so are not transported to distal sites within the body
What are the 3 principal eicosanoids?
- Prostaglandins
- Thromboxanes
- Leukotrienes
What is the main source of eicosanoids?
Arachidonic acid
What is arachidonic acid?
A 20 carbon unsaturated fatty acid containing 4 double bonds
What is the initial and rate-limiting step in eicosanoid synthesis?
Liberation of arachidonic acid by phospholipase A2 (PLA2)
How is PLA2 activated?
PLA2 is activated by a variety of receptor-mediated signals
What are the two ways that we can metabolise arachidonic acid to synthesise eicosanoids and which type does each synthesise?
- Cyclo-oxygenase and peroxidase to give prostaglandins and thromboxanes
- Lipoxygenases to give leukotreines
What can prostaglandins do?
- Vasoconstriction/dilation
- Inhibit/promote platelet aggregation
- Effects depend upon receptor (e.g. EP1 receptor - vasoconstriction; EP2 receptor - vasodilation)
- Inflammatory response, thermoregulation and pain
Where are thromboxanes synthesised?
In platelets