Membranes and Lipids 2 Flashcards
What are the five methods of intercellular communication?
- Autocrine - The cell that secretes the signal also expresses the receptor. It can therefore self activate or self inhibit.
- Paracrine - The secretory cell and target cell are in close proximity e.g. in the same tissue. The signal can therefore diffuse across to the target cell and then bind with the receptor.
- Juxtacrine - The secretory cella and the target cell are in contact and therefore can form channels between them. The cells come up against each other and connexions in the membranes form a pore to allow movement of molecules e.g. in cardiomyocytes and immune cells
- Endocrine - The signal enters the bloodstream and so can travel long distances to the target cell.
- Neural - The electrical signal is converted to a chemical signal before when transmitted to the second neurone.
- Neuronal -
What are the 4 receptor superfamilies?
- Ligand-gated ion channels
- G-proteins coupled receptor
- Receptor tyrosine kinases
- Nucelar hormone receptors
Give the structure, role and signalling mechanism employed by the 4 receptor superfamilies and give an example of specific receptor within each superfamily.
- Ligand-gated ion channels
Binding of the ligand to the receptor opens the channel very quickly. Therefore very common in excitable cells such as neurones. Important especially in depolarisation and hyper polarisation of neurones.
The binding of the ligand to the receptor results in a conformational change in the shape of the channel enabling it to open.
E.g. Nicatinic-acetylcholine receptor. Acetylcholine binds to the receptor opening the channel enabling the movement of sodium and potassium ions into the neurone.
Give the structure, role and signalling mechanism employed by the 4 receptor superfamilies and give an example of specific receptor within each superfamily.
- G-protein coupled receptor
The receptor is made up of 7 transmembrane domains. The N-terminus is outside the cell and the C-terminus is inside the cell. The binding of the ligand to the receptor activates the G-protein.
Targets of this receptor include peptide hormones such as Insulin and neurotransmitters. The Muscarinic acetylcholine receptor is a G-protein coupled receptor.
Give the structure, role and signalling mechanism employed by the 4 receptor superfamilies and give an example of specific receptor within each superfamily.
- Receptor tyrosine kinases
Single transmembrane helix with the N-terminus outside the cell and C-terminus inside. The C-terminus has a catalytic domain and so can act as an enzyme. Non-catalytic receptors can bind to other proteins that can transmit the signal.
The ligands binds to the receptor and then the two receptors come together - dimerise. The protein kinase of each receptor monomer then phosphorylates a distinct set of tyrosine residues in the cytosolic domain of its dimer partner. This causes activation downstream leading to changes in gene expression and protein secretion. Slower than ligand-gated ion channels.
Example: Insulin
Give the structure, role and signalling mechanism employed by the 4 receptor superfamilies and give an example of specific receptor within each superfamily.
- Nuclear hormone receptor
Found inside the cell as the ligands can pass through the bilayer. The receptor has a ligand binding domain and a DNA binding domain. As a result the ligand can act as a transcription factor. The receptor can be in the cytosol or in the nucleus. This leads to binding to specific sites within the promoter region known as hormone responsive elements.
Examples of ligands include steroid hormones and thyroid hormones.
Give the major types of neurotransmitters.
- Monoamines e.g. Dopamine, Histamine, Serotonin and Adrenaline
- Amino acids e.g. glutamate, aspartate, GABA, glycine
- Lipids e.g. Anandamide
Give the major types of hormones.
- Hydrophillic hormones
- Catecholamines e.g. adrenaline, noradrenaline
- Peptide hormones
e. g. insulin, glucagon and angiotensin II - Lipid based hormones
- Steroid hormones e.g. oestrogen and testosterone
- Thyroid hormones e.g. Thyroxine
- Sterol hormones e.g. Calcitrol (Vitamin D)
How does the signal transmit between neurones?
- The neurotransmitter is synthesised from precursor molecules and stored in vesicles.
- When the signal is released calcium ion channel opens leading to an influx of calcium and so the depolarisation of the membrane.
- This causes vesicles continuing the neurotransmitter to fuse with the membrane and so the neurotransmitter released by exocytosis.
- This activates receptors on the post-synaptic neurone.
Give the life cycle of a neurotransmitter and how this can be targeted in the treatment of depression (i.e. the sites of antidepressant drug action)
There are two main mechanisms to get rid of the neurotransmitters in the synaptic cleft and therefore inactivate the post-synaptic neurone.
- Re-uptake of the neurotransmitter in the presynaptic neurone.
- Degradation by enzymes.
Some drugs target the neurotransmitters in the synaptic cleft. SSRIs reduce the uptake of serotonin in the treatment of depression. Other treatments fo depression include monoamine oxidase inhibitors (MAOI), SNRIs (Serotonin Noradrenaline Re-uptake Inhibitors), electro-convulsive therapy and mood stabilising drugs.
What is the signalling mechanism of gasotransmitters?
Gasotransmitters are small gases such as CO, NO and H2S which can pass across the bilayer and cause change in a cell. These are important in paracrine signalling. Carbon monoxide is a gasotransmitter that is produces in the liver in small doses.
What are the general features of signal transduction pathways and what give rise to these features?
- Specificity - The first messenger is specific to the receptor. Binding may to different receptors may elicit different responses. Cross talk also can occur.
- Hierarchy - The components of age signal transduction pathway are arranged in a specific order to transmit the signal inside the cell.
- Amplification - The main sources of amplification are at the level of the effector enzyme, the kinase enzyme and at the level of the G-protein - this is as one receptor can activate multiple G-proteins.
- Complexity - There are many different G-proteins, kinase enzymes and cross-talk can occur.
What are the main types of `G-proteins? What is their effect?
G-proteins are hetratrimeric. There are 3 subunits in the G-protein - G-alpha, G-beta and G-gamma subunits.
There are many types of G-alpha subunits. Specific subunits act on different effector enzymes.
Gs - Act on Adenylate Cyclase. Stimulate the increase in production of cAMP.
Gi - Act on Adenylate Cyclase and inhibit the production of cAMP.
Gq - Act of Phospholipase C and increase the production of DAP and IP3.
How is the activity of G-proteins regulated?
G-proteins when inactivated are bound to GDP. In order to activate the protein GDP is phosphorylated to GTP. G-proteins have an intrinsic GTPase activity and so are able to self-activate and self-deactiave.
What is the effect of the Cholera Toxin and the Pertussis toxin on different G-proteins? How does this contribute to clinical symptoms?
The cholera toxin reduces the GTPase activity of the Gs protein. It means the the Gs protein cannot convert GTP to GDP. As a result, the Gs protein cannot turn off leading to an increase in cAMP. This therefore means that the intestinal cells keep their chloride ion channels open. This leads to a loss of chlorine from the intestine and so water being drawn into the intestine. Sodium re-uptake is reduced leading to severe dehydration and diarrhoea.
The Pertussis toxin acts on the Gi toxin. It prevents the Gi protein from converting GDP to GTP. As a result, the Gi protein cannot turn on leading to an accumulation of cAMP. This can lead to the increased production of histamine, and so localised inflammation.
