Cell Signalling Flashcards
How does neurotransmission work
1) Action potential is propagated by voltage gated sodium channels opening.
Sodium influx causes membrane depolarization so action potential moves alone neurons
2) action potential opens voltage gated calcium ion channels at oresynaltuc terminal. Calcium ion influx causes vesicle exocytosis
3) postsynaotic receptors are activated
NTbinds to receptors on the post synaptic membrane
4 reasons for cell communication
Process information-sensory stimuli
Self preservation-spinal reflexes
Voluntary movement
Homeostasis- thermoregulation and glucose homeostatic
What are the 2 main systems that provide communication lines
1) nerve fibers of the CNS and PNS provide a rapid response
2) blood vessels of the cardiovascular system provide a slower but more versatile repo se
What is endocrine signalling
Hormone travels within blood vessels to act on a distant target cell
Glucagon secreted by alpha cells stimulating glycogenolysis and gluconeogenesis
Adrenaline produc3 in adrenal glands act on trachea
What is paracrine signalling
Hormone acts on an adjacent cell
Insulin has a paracrine affect by inhibiting glucagon
Nitric oxide made by endothelial cells in blood cause vasodilation
Osteoclast activating factors produced by adjacent osteoblasts
What is autocrine signalling
Signalling molecule acts on the same cell
Activated T cell receptors initiate a cascade of reactions within the T cell and the expresses interleukin 2(IL-2) receptor on its surface.
Also secretes IL2 which binds to its receptors on the same cell
Acetylcholine binds to presynaptic M2 muscarinic receptors
Growth factors from tumour cells can bind to and act on tumour cells to cause mitogenesis
Signalling between membrane attached protein
Where plasma membrane proteins on adjacent cells interact
Ligands attached on one cell can trigger signalling on an adjacent.cell
How does signalling work with virus detection and immune response
1) Bloodborne virus (e.g. hep C) detected in bloodstream by APC
- HIV GP120 glycoprotein binds to CD4 receptors on T lymphocytes
- Bacterial cell wall components bind to toll-like receptors on haematopoietic cells
2) APC digests pathogen and expresses major histocompatibility complex 2 (MHC II) molecules on its surface
3) Circulating T lymphocytes engage with MHC molecule through T-cell receptor (TCR) interaction
What are ligands
Chemical messages that exert their effects through binding to receptors which are usually proteins this activates the receptors
What are second messengers
Cause intracellular effects that are evoked by activated receptors
Ligand gated ion channels
Signal transduction event
1) Ligand binds to receptor protein
2) Change in conformation of channel protein leads to opening of a pore
3) Pore allows ions to move in/out of cell according to their respective conc gradients
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Examples of ligand gated ion channels-ionotrophic receptors
Nicotinic ACh:Muscle contraction and cognitive enhancement
GABA A:inhibition of neuronal activity
NMDA:synaptic plasticity and membrane formation
5-HT3 :anxiety ,emesis
What is the G protein coupled receptor made up of
7-transmembrane receptors because the channel protein crosses cell membrane seven times
Are linked to intracellular G protein complex made up of alpha subunit beta gamma subunit and associated gdp molecule
How does G protein work
1) 7-TM receptor and heterotrimeric G protein are inactive in resting state
2) Ligand binding causes conformational change of receptor
3) Unassociated G-protein binds to receptor and bound GDP molecule is phosphorylated to GTP
4) G-protein dissociates into 2 active components: α subunit and βγ (beta-gamma) subunit which act as secondary messengers- α subunit binds to target protein
5) Receptor remains active as long as ligand is bound and can activate further heterotrimeric G-proteins rather than just 1
6) When ligand dissociates from receptor, internal GTPase activity on α subunit dephosphorylates GTP to GDP
7) α subunit dissociates from target protein- becomes inactive again and binds to a Gβγ subunit
Examples of G protein coupled receptor
Beta 1-adrenergic receptor
Muscarinic M2 receptor
dopaminergic receptor
AT-1 receptor (angiotensin 1 receptor)
3 subtypes of GPCRS
- Gs Protein linked receptor- explain how it works and give an examplestimulates adenyl cyclase which, converts ATP into cAMP, which activates protein kinase Ae.g. Beta 1-adrenergic receptor
- Gi Protein linked receptor- explain how it works and give an exampleinhibits adenyl cyclase, therefore inhibits protein kinase AMuscarinic M2 receptor
- Gq Protein linked receptor- explain how it works and give an examplestimulates phospholipase C which converts PIP2 to IP3 and DAG
IP3 stimulates Ca2+ release
DAG activates protein kinase CAT-1 receptor (angiotensin 1 receptor)
Which terminus of the 7-TM proteins does the extracellular ligand bind to
N terminus
Which terminus of the 7-TM proteins does the intracellular G protein bind to
C terminus
Enzyme linked receptor
1) ligand binding leads to receptors clustering
2) This activates enzyme activity within cytoplasm that phosphorylate receptor
3) This phosphorylation causes binding of signalling proteins to cytoplasmic domain of the receptor
4) These signalling proteins recruit other ones leading to a signal being generated within the cell
5) Signal is terminated when a phosphatase dephosphorylates the receptor
Examples:insulin receptor, ErbB receptor,NPR1,TGF-beta R1
Enzyme linked receptors roles
Insulin used for glucose uptake and lipid metabolism. Antigen js CD220
PR1 used in vasodilation and reduction in blood pressure
TGFbR1 used in apoptosis
ErbB receptor- ligand js epidermal growth factor causes cell growth and proliferation
Intracellular receptors
Cytoplasmic and nuclear
1) located in cytosol
2)associated with chaperon molecules
3)hormone binds to receptors causing hsp to dissociate
4)2 hormone bound receptors form a homodimer
5) homodime translocated to nucleus and binds to DNA and acts as a transcription factor
Nuclear is located in nucleus and bound to DNA the binding of hormone ligand leads to transcriptional regulatio
Examples of nuclear and cytoplasmic receptors
Glucocorticoid receptor and estradiol receptor for cytoplasmic
Thyroid
