2.9 - Cell Signalling Flashcards
1
Q
Why do cells need to communicate?
A
- to process information (sensory stimuli e.g. light and sound)
- self-preservation (identify danger and take appropriate actions e.g. spinal reflexes and sympathetic NS) - innate
- voluntary movement
- homeostasis (e.g. thermoregulation, BGC)
2
Q
Endocrine signalling
A
Hormone travels within blood vessels to act on a distant target cell
- e.g. glucagon is secreted by alpha cells of Islets of Langerhans and travels out of pancreas in blood vessels, stimulating gluconeogenesis and glycogenolysis within the liver = increased BGC
- e.g. insulin produced in the pancreas acts on the liver, muscle cells and adipose tissue
- e.g. adrenaline produced in the adrenal glands acting on the trachea
3
Q
Paracrine signalling
A
Hormone acts on an adjacent cell
- e.g. insulin produced by beta cells in response to hyperglycaemia acts on alpha cells to inhibit glucagon secretion
- e.g. nitric oxide produced by endothelial cells in blood vessels, acts on smooth muscle cells = vasodilation
- e.g. osteoclast activating factors produced by adjacent osteoblasts
4
Q
Signalling between membrane-attached proteins
A
Plasma membrane proteins on adjacent cells interacting
- e.g. TCR interacting with MHC class II molecule - blood borne virus detected within bloodstream by APC, which digests pathogen = expresses MHC class II molecules on surface, circulating T cell engages with MHC through TCR interaction
- e.g. HIV GP120 glycoprotein interacts with CD4 receptor on T cells
- e.g. bacterial cell wall components binding to toll-like receptors on haematopoietic stem cells
5
Q
Autocrine signalling
A
Signalling molecule acts on same cell
- involved in positive or negative feedback
- e.g. interleukin-2 acting on T lymphocytes - activated T cell expresses interleukin-2 which binds to IL-2 receptor on same cell
- e.g. acetylcholine acting on presynaptic M2 muscarinic receptors
- e.g. growth factors (e.g. TGFB) from tumour cells leading to mitogenesis
6
Q
Neurotransmission (intracellular signalling)
A
- Propagation of action potential
- AP propagated by VGSCs opening
- Na+ influx –> membrane depolarisation –> AP ‘moves along’ neurone
- VGKC opening –> K+ efflux –> repolarisation - 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 postsynaptic membrane
- receptors modulate postsynaptic activity
- the signal can be transmitted by a variety of different types of receptor
7
Q
Ionotropic receptor
A
- ligand (molecule which binds to receptor) binds to receptor protein
- change in conformation of channel protein –> opening of pore
- pore allows ions to move in and out of cell according to their respective concentration gradients
- e.g. nicotinic acetylcholine
- ligand - acetylcholine
- location - skeletal muscle
- physiological effect - muscle contraction
8
Q
G-protein coupled receptor
A
- ligand binding –> activates intracellular G protein
1. in resting state the G protein complex consists of a Ga subunit, GBy subunit and an associated GDP molecule, which are in close proximity to the receptor. 7-transmembrane receptor and heterotrimeric G-protein are inactive
2. ligand binding –> changes conformation of receptor
3. unassociated G-protein binds to the receptor –> GDP is exchanged for GTP (allows heterotrimer to dissociate)
4. G-protein dissociates into two active components: a-subunit and By subunit (GTP stays attached to alpha component). They bind to their target proteins and both can act as second messengers
5. internal GTPase activity on a-subunit dephosphorylates GTP –> GDP
6. a-subunit dissociates from target protein –> inactive again = heterotrimer reformed as Ga and GBy reassociate
7. receptor remains active as long as ligand is bound and can activate further heterotrimeric G-proteins
9
Q
Examples of G-protein coupled receptors
A
- Gs protein linked receptor - stimulates adenylyl cyclase
- converts ATP to cAMP, which activates protein kinase A (PKA)
- e.g. B1-adrenergic receptor (fight / flight) - Gi protein linked receptor - inhibits adenylyl cyclase
- reduces levels of PKA
- e.g. M2-muscarinic receptor (rest / digest) - Gq protein linked receptor - stimulates phospholipase C (PLC)
- converts PIP2 –> IP3 + DAG
- IP3 stimulates CA2+ release
- DAG activates PKC
- e.g. AT-1 angiotensin receptor
10
Q
Enzyme-linked receptor
A
- ligand binding –> receptor clustering
- activates internal enzyme activity within cytoplasmic domain
- enzymes phosphorylate receptor
- phosphorylation –> binding of signalling proteins to cytoplasmic domain
- these signalling proteins –> recruit other signalling proteins –> signal is generated –> cascade
- e.g. insulin receptor (CD220 antigen): ligand - insulin; physiological effect - glucose uptake
- e.g. ErbB receptors: ligand - epidermal growth factor, transforming growth factor B; physiological effect - cell growth and proliferation
11
Q
Intracellular receptor - Type 1
A
- a membrane permeable ligand binds to receptor inside cell
Type 1 - cytoplasmic
1. located within cytosolic compartment
2. associated with chaperone molecules (heat shock proteins / HSP)
3. hormone binds to receptor –> HSP dissociates
4. two hormone bound receptors form a homodimer
5. the homodimer translocates to the nucleus –> binds to DNA - e.g. glucocorticoid receptor
- ligands: cortisol, corticosterone
- physiological effect: reduced immune response, increased gluconeogenesis
12
Q
Intracellular receptor - Type 2
A
Type 2 - nuclear
1. located within the nucleus
2. binding of hormone ligand (directly to nucleus) –> transcriptional regulation
- e.g. thyroid hormone receptor
- ligand: thyroxine (T4), triiodothyronine (T3)
- physiological effect: growth and development