Cell Signalling Flashcards
Why do cells need to communicate?
- Process information - Sensory stimuli (e.g. sight, sound)
- Self preservation - Identify danger & take appropriate actions (Spinal reflexes, Sympathetic nervous system)
- Voluntary movement - Getting from A to B, Completing daily tasks
- Homeostasis - Thermoregulation, Glucose homeostasis
What is an example of endocrine communication?
The physiological response to hypoglycaemia is glycogen breakdown and gluconeogenesis. The process for that: Glucagon is secreted by a-cells of Islets of Langerhans (in pancreas). Travels out of pancreas in blood vessels and stimulates glycogenolysis & gluconeogenesis within the liver ® increasing blood glucose levels.
What is endocrine signalling and what are examples of it?
Hormone travels within blood vessels to acts on a distant target cell. Examples are: Insulin produced in the pancreas acts on the liver, muscle cells & adipose tissue; Adrenaline produced in the adrenal glands acting on the trachea.
What is an example of paracrine communication?
The response to hyperglycaemia is an example of paracrine communication. Increased blood glucose - insulin secretion by b- cells in the Islets of Langerhans. Insulin has paracrine effects by inhibiting glucagon secretion. Insulin also has endocrine effects on the liver
What is paracrine signalling and what are examples of it?
When a hormone acts on an adjacent cell. Examples are: Nitric Oxide produced by endothelial cells in blood vessels, Osteoclast activating factors produced by adjacent osteoblasts.
Provide examples of signalling between membrane attached proteins
- Blood borne virus (e.g. Hepatitis C) detected within blood stream by antigen presenting cell (APC)
- APC digests pathogen expresses major histo-compatibility (MHC) class II molecules on surface
- Circulating T-lymphocyte engages with MHC molecule through T-cell receptor (TCR) interaction
What is autocrine signal? Provide an example.
Signalling molecule acts on same cell. Activated TCR will initiate a cascade of reactions within T-cell.
Activated T-cell expresses interleukin-2 (IL-2) receptor on surface. Activated T-lymphocyte also secretes IL-2, which:
1. Binds to IL-2 receptor on same cell
2. Binds to IL-2 receptor on adjacent activated T-cell
What is neurotransmission an example of and how does it work?
Neurotransmission is an example of paracrine signalling. There are 4 steps to neurotransmission:
- Propagation of action potential
- AP is propagated by VGSCs opening
- Na+ influx —-> membrane depolarisation —-> AP ‘moves along’ neurone
- VGKC opening —> K+ efflux —-> Repolarisation - Neurotransmitter (NT) release from vesicles
- AP opens voltage-gated Ca2+ channels at presynaptic terminal
- Ca2+ influx —> vesicle exocytosis - Activation of postsynaptic receptors
- NT binds to receptors on post-synaptic membrane
- Receptors modulate post-synaptic activity - Activation of postsynaptic receptors
- The signal can be transmitted by a variety of different types of receptor
What are the different types of receptors?
- Ionotropic receptor - Ligand binding —> opens ion permeable pore traversing the membrane
- G-protein coupled receptor - Ligand binding —-> activates intracellular G-protein
- Enzyme-linked receptor - Ligand binding —> receptor clustering ® activates internal enzymes 4. Intracellular receptor - A membrane permeable ligand binds to receptor inside cell
How do ionotropic receptors work? Provide an example and its effects
Carry out single transduction events. Firstly, ligand binds to the receptor protein causing a change in conformation of channel protein leading to opening of a pore. Pore allows ions to move in or out of cell according to their respective concentration gradients Example: Nicotinic Acetylcholine Ligand: Acetylcholine (ACh) Location: Skeletal muscle Physiological effect: Muscle contraction
How do G-Protein coupled receptors work?
Carry out single transduction events. 7-TM receptor & heterotrimeric G-protein are inactive. Ligand binding changes conformation of receptor. Unassociated G-protein binds to the receptor and bound GDP molecule is phosphorylated to GTP or GDP is exchanged for GTP (more correct as an explanation)
G-protein dissociates into two active components:
1. a-subunit
2. bg subunit
These bind to their target proteins. Internal GTPase activity on a-subunit dephosphorylates GTP ® GDP
a-subunit dissociates from target protein and is inactive again. Receptor remains active as long as ligand is bound and can activate further heterotrimeric G-proteins.
What are the types of G-protein linked receptors?
- Gs protein linked receptor - Stimulates adenylyl cyclase: Converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). cAMP activates protein kinase A (PKA) Example: b1-adrenergic receptor
- Gi protein linked receptor - Inhibits adenylyl cyclase: Reduces levels of PKA. Example: M2-muscarinic receptor
- Gq protein linked receptor - Stimulates phospholipase C (PLC): Converts PIP2 to IP3 and DAG
IP3 stimulates Ca2+ release (Note an increase in Ca2+ generally tends to cause some kind of contraction). DAG activates PKC. Example: AT-1 angiotensin receptor
How do enzyme-linked receptors work?
Ligand binding causes receptors clustering. Receptor clustering activates enzyme activity within cytoplasmic domain. Enzymes phosphorylate receptor. Phosphorylation leads to binding of signalling proteins to cytoplasmic domain. These signalling proteins recruit other signalling proteins so signal is generated within cell.
Give examples of enzyme receptors
Insulin receptor (CD220 antigen)
Ligand: Insulin
Physiological effect: Glucose uptake
ErbB receptors
Ligand: Epidermal Growth Factor, Transforming Growth Factor b
Physiological effect: Cell growth, proliferation
What are the two types of Intracellular receptors? Describe their properties
Cytoplasmic and Nuclear.
Type 1 - Cytoplasmic
Located within the cytosolic compartment. Associated with chaperone molecules (heat shock proteins, hsp) Hormone binds to receptor and hsp dissociates. 2 hormone bound receptors form a homodimer. The homodimer translocates to the nucleus and binds to DNA.
Type 2 - Nuclear
Located within the nucleus. Binding of hormone ligand causes transcriptional regulation,
