Cell signalling Flashcards
Why is cell signalling important for processing information?
Human body receives millions of inputs for many sources each day so it must be able to:
detect inputs
process information
manufacture an appropriate response
Why is cell signalling important for self- preservation?
Most innate response from external stimulus is for self-preservation e.g. spinal reflex arc
However threatening stimulus may require coordinated movement of a number of areas
Why is cell signalling important for voluntary movement?
For average individual voluntary movement is required to perform daily tasks
Why is cell signalling important for homeostasis?
Brain must be able to communicate will all organs, tissues and cells to maintain homeostasis
Although the brain is the central processing unit it does outsource certain tests e.g. parathyroid glands responsible for regulating calcium levels
What are 2 main systems which provide lines of communication?
Nerve fibres of central and peripheral nervous system - rapid and has instantaneous response
Blood vessels of cardiovascular system - slower, more versatile regulation
How is neurotransmission used for signaling?
- Propagation of AP
- AP propagated by VGSCs opening
- Na+ influx, membrane depolarisation, AP moves along neurone
- VGKC opening, k+ efflux, repolarisation - Neurotransmitter release from vesicles
- AP opens VGCCs 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
- signal can be transmitted by a variety of different types of receptors
What is the physiological response to hypoglycaemia?
Glycogen breakdown (glycogenolysis) Gluconeogenesis
- glucagon is secreted by alpha cells of islets of Langerhans
- glucagon travels out of pancreas into blood vessels
- glucagon stimulates glycogenolysis and gluconeogensis within liver increasing blood glucose levels
What is the physiological response to hyperglycaemia?
Glucose uptake Reduced gluconeogensis Reduced glycolysis 1. Increased blood glucose levels detected and insulin secreted by beta cells in islets of Langerhans 2. Insulin has paracrine effects: - inhibits glucagon secretion - also has endocrine effect on liver
How does paracrine signalling differ?
Acts on adjacent cells
e. g.
- nitric oxide produced by endothelial cells in blood vessels
- Osteoclast activating factors produced by adjacent osteoblasts
How do membrane proteins signal when a pathogen is detected?
- Blood bourne virus detected in blood by antigen presenting cell
- APC digests pathogen and expresses MHC class II on surface
- Circulating T lymphocyte engages with MHC through T cell receptor interaction
e.g. HIV GP120 glycoprotein interaction with CD4 receptor
How is autocrine communication used for cell signalling in T cells?
Activated TCR will initiate a cascade of reactions within T cell
Activated T cell express IL-2 on surface
Activates T cell will also secrete IL-2 which:
- binds to IL-2 receptor on same cell
- binds to IL-2 receptor on adjacent activated T cell
What are receptors?
They’re usually proteins which bind to ligands and elicit an effect in a cell upon activation
What is a second messanger?
A chemical messenger thats separate from the receptor which causes an intracellular effect to be evoked by the occupied receptor
What are the 4 categories of receptors?
Ligand-gated ion channel receptor
Enzyme linked receptors
G protein coupled receptors
Intracellular receptors
How do ligand- gated ion channel (inotropic) receptors work?
- Ligand binds to receptor protein
- Change in confirmation of channel protein- opening of a pore
- Pore allows ion to move in or out of cell according to its conc. gradient
What are examples of ligand- gated ion channel (inotropic) receptors?
Nicotinic ACh, ligand is Ach
GABAa, ligand is GABA
NMDA, ligand is glutamate
5-HT3, ligand is 5-HT
How do G protein coupled receptors work?
- 7-TM receptor and heterotrimeric G-Protein are inactive
- Ligand binding and change in confirmation of receptor
- Unassociated G protein molecule is phosphorylated to GTP or GDP is exchanged for GTP
- G protein dissociates into 2 active components:
- alpha subunit
- beta gamma subunit
these bind to target protein - Internal GTPase activity on alpha subunit dephosphorylates GTP to GDP
6, alpha subunit dissociates from target protein and is inactivated again - Receptor remains active as long as ligand is bound and can activate further heterotrimeric G-proteins
What type of G-Protein linked receptors are there?
Gs protein linked receptor: stimulates adenyl cyclase -converts ATP to cAMP -cAMP activates protein kinase A (pKA) e.g. B1- adrenergic receptor
Gi protein-linked receptor
inhibits adenyl cyclase
- reduces levels of pKA
e.g. M2- muscarinic receptor
Gq protein- linked receptor stimulates phospholipase C (PLC) - converts PIP2 to IP3 and DAG -IP3 stimulates Ca2+ release -DAG activates pKC e.g. AT-1 angiotensin receptor
How do enzyme linked receptors work?
- Ligand binding causes receptor clustering
- Receptor clustering activates enzyme activity within cytoplasmic domain
- The enzyme phosphorylates the receptor
- Phosphorylation leads to binding of signal proteins generated in cell
- signalling proteins recruit other signalling proteins- signal generated within cell
- Signal is terminated once a phosphate dephosphorylates the receptor
What are examples of enzyme-linked receptors?
Insulin: enzyme is tyrosine kinase, ligand is insulin
NPR1: enzyme is GC, ligand is ANP and BNP
TGF beta R1: enzyme is Ser/Thr kinase, ligand is TGF beta
How do intracellular receptors work?
Type 1- cytoplasmic:
- Located within cytosolic compartment
- Associated with chaperone molecules (heat shock proteins, hsp)
- Hormone binds to receptor- hsp dissociates
- 2 hormone bound receptors form a homodimer
- the homodimer translocates to the nucleus- binds DNA
Type 2- Nuclear
- located within nucleus
- binding of hormone ligand- transcriptional regulation
What are examples of type-1 intracellular receptors?
Glucocorticoid receptor
Ligand is cortisol and corticosterone
What are examples of type 2 intracellular receptors?
Thyroid hormone receptor
ligand is Thyroxine (T4), triiodothyronine (T3)
