Cell signalling Flashcards
Why do cells need to communicate?
Process information - sensory stimuli
Self preservation - fight or flight - spinal reflexes for sympathetic nervous system
Voluntary movement
Homeostasis - thermoregulation/glucose homeostasis
Hypoglycaemia is an example of?
Endocrine communication - leads to glycogen breakdown + gluconeogenesis
Glucagon secreted by a cells in pancreas ; glucagon travels out of pancreas in blood vessels and stimulates both processes within the liver
Endocrine signalling
When a hormone travels via blood from organ to another organ
Insulin
Another type of endocrine signalling ; acts on muscle/adipose tissue/liver
Adrenaline
Acts on trachea - endocrine signalling
Hyperglycaemia - mechanism of insulin can also be?
PARACRINE SIGNALLING - insulin secretion via b cells and acts on alpha cells next to it to inhibit glucagon secretion (as well as endocrine function in the liver)
Paracrine signalling?
Hormone acts on adjacent cells
Other examples of paracrine signalling
Nitric oxide produced by endothelial cellist blood vessels- vasodilation (reduces blood pressure)
Osteoblast activating factors produced by adjacent osteoblasts
Osteoblast
Cell which secretes the substance of bone
Signalling between membrane attached proteins
The pathogen is detected by an APC which digests the pathogen and expresses the MHC class II molecule on the surface ; circulating T-lymphocyte engages with MHC through TCR
Membrane attached proteins
Plasma membrane proteins on adjacent cells interact
Examples of membrane attached proteins
HIV gp120 glycoprotein with CD4 receptor on T lymphocytes
Bacterial cell wall components detection ; using receptors on heatopoietic cells
Autocrine signalling with T cell
Activated TCR will initiate a cascade of reactions within T cell and that will express IL-2 receptor on surface
T cell secrete IL-2 molecules which can now bind to IL-2 receptors on the same cell and those on adjacent cells (paracrine)
Examples of autocrine
Acetylcholine -> presynaptic M2 muscarinic receptors
Growth factors from tumour cells leading to mitogenesis
Neurotransmission mechanism
Propagation of action potential by VGSCs ; NA+ influx leads to membrane depolarisation and there is then a K+ efflux
AP opens ca2+ channel at presynaptic terminal ; ca2+ influx causes acetylcholine exocytosis
NT binds to receptors on post synaptic neurone
Activation of post synaptic receptor
Post synaptic cell
Can be muscle neurone whatever
4 types of receptors
Ionotropic receptor - ligand binding causes ion permeable pore to open
G protein coupled receptor ; ligand binding activates intracellular G-protein
Enzyme linked receptor - ligand binding results in receptor clustering causing activation of internal enzymes
Intracellular receptor - membrane permeable ligand binds to receptor inside cell
Iontropic receptors
Ligand binds to receptor protein and this changes conformation of channel protein ; pore now allows ions to move in and out of cell (respective to conc gradients)
Ionotropic receptor example
Nicotinic Acetylcholine ; ligand is Ach ; located in the skeletal muscle and results in muscle conc
GABA channels
Ion channels
G-protein coupled receptors
Heterotrimeric G-protein ; alpha beta and gamma ; BETA AND GAMMA ALWAYS STICK TOGHETHER
80% of drugs target them
G-protein coupled receptors
Another word for a g-protein coupled receptor
Serpentine receptor
Mechanism of action of G protein coupled receptor
7-TM receptor and heterotrimeric G-protein are inactive
Ligand binds and changes conformation of receptor
Unassociated G protein binds to the receptor and GDP is exchanged for GTP which allows beta and gamma to separate from alpha and GTP
Alpha and gtp/beta gamma bind to their target proteins
GTPase acts on alpha subunit causing GTP to go to GDP and alpha unit dissociates from target protein to form the inactive heatertrimeric G protein
How long does the receptor remain active for in a G protein coupled receptor?
Receptor remains active as long as ligand is bound and can activate other heterotrimeric G-proteins tooooo
What is the target protein that is often targeted by the components of the heterotrimeric G protein?
Adenylyl cyclase
Example of a G protein linked receptor that stimulates adenylyl cyclase?
b-andrenergic receptor (this is how adrenaline acts on the heart) ; it converts ATP to cAMP which activates your protein kinase
G protein linked receptor that inhibits adenylyl cyclase
M2 muscarinic receptor (parasympathetic nervous system that is continuously keeping your heart rate down) ; this REDUCES levels of protein kinase A
Gs/Gi
Stimulatory/inhibitory G protein
Gq protein linked receptor
Phospholipase C is what GQ is linked to and this c causes an increase in calcium ; example is angiotensin receptor that causes vasoconstriction - so a common drug target is ACE inhibitors for hypertension
Enzyme linked receptors
Ligand binding externally causes receptors to cluster internally which activates enzymes in the cytoplasm ; these enzymes phosphorylate the receptor (which moves receptors into a high energy state) ; signalling proteins are now bound to the cytoplasmic domain (receptors)
Insulin receptor is also known as
CD220 antigen
Classify insulin receptor?
Enzyme-linked receptor with the ligand being insulin and effect being glucose uptake
ErbB receptors
The ligand is an epidermal growth factor/transforming growth factor which causes cell growth/proliferation
Intracellular receptors Type 1 is
Cytoplasmic ; receptor in cytosol and associated with heat shock protein ; hsp dissociates and 2 hormone bound receptors form a homodimer which translocates to the nucleus to bind with dNA
Intracellular receptor Type 2 is
Nuclear ; bind of hormone ligand to receptor in nucleus which now regulates transcription
intracellular receptors - glucocorticoid
Ligand is cortisol/corticosterone and this decreases immune response and increases gluconeogenesis
Intracellular receptors - thyroid hormone receptor
Thyroxine and triiodothyronine (T4 and T3) are ligands and the physiological response is growth and development
