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Cell communications
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- 1What is a ligand?A drug or neurotransmitter, something that binds to something else.
- 2What are 2 types of signalling?Endocrine signalling - signal molecule released from endocrine gland, hormone distributed throughout organism eg. adrenaline. 'long distance effect'
Paracrine signalling - local mediators/hormones secreted into interstitial fluid eg. histamine. 'localised response'. - 3What are another 2 types of signalling?Neuronal signalling - NT released from a neuron affecting adjacent cells - eg. acetylcholine.
Contact dependent signalling - where a component of one membrane signals to a protein in the membrane of an adjacent cell. eg delta (protein). Most specific signalling between cells. - 4What are the 6 types of signal molecule?- Simple (nitric oxide NO)
- Complex (insulin -dipeptide with 51 amino acid residues)
- Peptides/proteins
- Fatty acid derivatives
- Cholesterol derivatives
- Amino acids and their derivitives - 5What are 2 ways in which signal molecules can be removed?- Spontaneous breakdown (NO is labile so it is rapidly converted into a nitrate ion without the requirement for an enzyme)
- Enzymic breakdown (acetylcholine is degraded to acetate and choline by cholinesterase; peptides and proteins may be degraded by proteases and peptidases). - 6What are another 2 ways in which signalling molecules can be removed?- Reuptake (neurotrasmitters such as adrenaline, GABA, glycine, dopamine are removed by efficient transport systems.
- Receptor internalisation (some ligands are internalised along with their receptors after binding) - 7How does rate of removal effect the field of influence?- NO is rapidly oxidised to nitrate so will not travel far from its site of release = local mediator.
- Similarly with acetylcholine
- Noradrenaline is removed much more slowly and therefore affects a range of tissues throughout the body. - 8How does rate of removal affect duration of action?- Signals mediated through acetylcholine can be turned on and off very rapidly = essential for coordination of movement.
- Throxine (hormone) has a half life of DAYS = its influence is felt for days after its release. - 9What are the two main types of receptor?- Cell surface receptors - water soluble polar signal molecules cannot enter the cell.
- Intracellular receptors - hydrophobic signal molecules can enter the cell because the cell membranes present no barrier to their ligands. - 10What is signal transduction?- Process by which the external signal (ie. presence of a signal molecule) is conveyed to the cell.
For cell surface receptors this usually involves a conformational change being conveyed across the membrane.
The internal conformational change may lead to an internal signal molecule (secondary messenger). - 11What is an example of a non-polar (hydrophobic) signalling molecule?- Nitric oxide.
- Because it is hydrophobic it cannot be 'trapped' within vesicles and therefore cannot be stored. Therefore its synthesis marks its release.
- Immediately leaves site of synthesis and affects adjacent cells. - 12How does NO signalling work?- NO is involved in controlling the diameter of blood vessels.
- Arteries are lined with endothelial cells.
- Stimulation by acetylcholine activates nitric oxide synthase (NOS) in these cells.
- NO causes relaxation of the smooth muscle surrounding these blood vessels. - 13How does NO signalling work (continued)- Target for the NO is guanylate cyclase. NO binds to the active site of guanylate cyclase, activating it.
- The cGMP produced causes the relaxation.
- Cyclic GMP activates a protein kinase. This kinase then phosphorylates proteins causing a conformational change and MUSCLE RELAXATION. - 14How is the NO signal terminated?- NO is rapidly oxidised to nitrate.
- cGMP is converted to GMP by the action of cGMP phosphodiesterase - breaks the phosphodiester bond with the 3' OH of ribose. - 15How do steroids bind their receptors?- Steroid hormones are also hydrophobic.
- They readily diffuse across membranes and their receptors are soluble cytoplasmic proteins.
- Binding of the ligand to its receptor unmasks the nuclear targeting signal and a DNA binding site (=conformational change).
- The steroid-receptor complex regulates gene expression. - 16What is the mechanism of action of thyroxine?- Thyroxine/triiodothyronine work in a similar way to steroid hormones, but their receptors are already located in the nucleus.
-The nuclear membrane presents no barrier to these ligands. - 17What effect do mutated androgen (testosterone) receptors have on the individual?- The individual (Male XY) is incapable of signal transduction. They are biologically male (internal testes instead of ovaries) but outwardly female.
- No functioning receptors = the masculating influence of testosterone is without effect on the foetus and in later life. - 18What are the 3 major classes of receptors?- Ligand-gated ion channels (eg. nicotinic acetylcholine receptor)
- G-protein linked receptors (beta-adrenergic receptor)
- Enzyme-linked receptors - (growth factor receptors) - 19What is a superfamily?Group of related proteins identified by their sequence similarity and presumed to have evolved from a common ancestor.
- 20Name 5 ligand-gated ion channels in the ligand-gated ion channels superfamily.- Nicotinic acetylcholine receptor
- Glutamate receptor
- 5-hydroxytryptamine (5HT) receptor
- GABA receptor
- Glycine receptor
(G-protein linked receptors exist for all of these ligands EXCLUDING glycline). - 21What is the structure of an example ligand-gated ion channel?- 5 polypeptides
- Each polypepide contains 1 amphipathic helix and 5 subunits produce a channel across the membrane = TRANSVERSE.
- Conformational changes on binding of 2 aceylcholine molecules to the 2 alpha-subunits = transient opening of the channel to cations.
- Similar events occur in other members of this superfamily. - 22What is the effect of channel opening on membrane potential?- Opening Na+ channels will depolarise the cell as the membrane potential and sodium gradient result in Na+ entering the cell.
- Opening K+ channels will hyperpolarise the cell as K+ leaves the cell.
- Opening Cl- channels will hyperpolarise the cell as Cl- enter. - 23How do voltage - gated ion channels work?- When Ach receptors are opened the membrane becomes depolarised.
- If sufficient numbers are opened, adjacent VDGC Na+ channels are activated.
- VDGCs sense the depolarisation of the membrane and transiently open causing a wave of depolarisation (the action potential) to sweep through the cell membrane, triggering events in distant parts of the cell. - 24What are some other examples of ligand-gated ion channels?- 5-HT3 receptors (cation channel)
- Ionotropic glutamate receptor (cation channel)
- GABAa receptor (chlorine channel)
- Glycine (chloride channel) - 25How many transmembrane-helices are present in a G-protein linked receptor?Seven
- 26How does a G-protien linked receptor work?- Ligand (eg. adrenaline) binds to extracellular surface and causes a conformational change in the 7-transmembrane helix receptor which is transmitted to the cytoplasmic domain.
- This internal conformational change activates a trimeric G-protein in the cytoplasm. - 27What is the structure of a G-protein?- Each G-protein is associated with a particular G-protein linked receptor.
- G-proteins are trimeric - alpha beta and gamma subunits.
- The alpha-subunit contains a GDP molecule bound to its active site and has no catalytic activity.
- Binding of the ligand to the receptor causes the alpha-subunit to exchange GTP for GDP and this results in the alpha subunit dissociating from the beta-gamma complex. - 28What are the targets for the activated alpha-subunit?- In the case of the beta-adrenergic receptor, the alpha-subunit of the activated G-protein activates a membrane bound enzyme adenylate cyclase.
- Adenylate cyclase converts ATP to the second messenger cAMP.
- cAMP activates a protein kinase called protein kinase A.
- cAMP binds to the regulatory subunits of protein kinase A, releasing the active catalytic subunits. - 29Give a summary of the actions of the second messenger, cAMP.- Ligands eg. adrenaline activate adenylate cyclase.
- cAMP activates cAMP dependent kinase (protein kinase A)
- Protein kinase A can phosphorylate enzymes and other proteins to modulate their activity.
- Protein kinase A can phosphorylate proteins involved in modulating transcription and turn on target genes. - 30Describe cAMP effects of protein activity compared to gene expression.- When cAMP alters protein activity the effects occur rapidly, whereas effects on gene expression take longer to become apparent (ie. takes longer because transcription/translation needs to take place).
- 31Targets of the activated G-protein alpha-subunit continued....- Acetylcholine can bind to a G-protein linked receptor (muscarinic acetylcholine receptor)
- In this case the activated alpha-subunit switches on the enzyme phospholipase C which generates IP3 and DAG from the lipid phophatidylinositol 4,5-bisphosphate (component of the lipid bilayer). - 32Inositol 1,4,5 trisphosphate (IP3) is a second messenger. Explain how it works.- IP3 releases Ca2+ from stores in the endoplasmic reticulum.
- Ca2+ + DAG activate protein kinase C attached to the plasma membrane.
- Protein kinase C activates a number of protein targets, including proteins involved in transcription (turning on the expression of particular proteins). - 33How does calcium work as an intracellular messenger?- Large number of cellular processes are modulated by calcium.
- Many of these effects are due to calcium binding to the protein calmodulin, which in its calcium-activated form activates a calmodulin dependent kinase (CaM - kinase).
- CaM kinase regulates the activity of many proteins including some involved in transcription. - 34Summarise the actions of IP3 and DAG.- Ligands such as acetylcholine, activate phospholipase C.
- IP3 opens Ca2+ channels in the ER.
- Ca2+ can activate many processes, mainly through its partnership with the calcium binding protein calmodulin.
- Ca2+ and DAG activate C kinase.
- Ca2+- calmodulin activates CaM- kinase. - 35How are these signals turned off?- Adrenaline reuptake/metabolism.
- Acetylcholine metabolism (Ach-esterase)
- G-alpha subunits have GTPase activity, converting (hydrolysing) the bound GTP tp GDP, resulting in the reformation of the inactive alpha-beta-gamma complex.
- Phosphodiesterase converts cAMP to AMP.
- IP3 and DAG are converted to inactive metabolites.
- Ca2+ pumped back into the endoplasmic reticulum.
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- Undergraduate Foundations of Physiology II Fichas sobre Cell communications, creado por imiheenan el 16/05/2015.
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