Cell Signalling Flashcards
Why do cells communicate
Process information
Self preservation such as reflex arcs
Voluntary movement
Homeostasis
What is endocrine communication and an exampl e
Hormone travels within blood vessels to act on a distant target cell
Insulin produces in the liver acts on the liver, muscle cells and adipose tissue
What is paracrine communication and an example
Hormones which act on adjacent cells
Insulin has paracrine effects, inhibiting glucagon secretion
What is signalling between membrane attached proteins?
Plasma membrane proteins on adjacent cells interacting
Eg Hiv with glycoprotein 120 binding to CD4 receptors on T lymphocytes
What is autocrine communication?
Signalling molecule acting on the same cell
Eg acetylcholine acting on presynaptic M2 muscarinic receptors
What are the 4 types of receptors?
Ionotropic receptors
G protein coupled receptors
Enzyme linked receptors
Intracellular receptors
3 signal transduction events of ionotropic receptors
And an example
Ligand binds to receptor protein
Change in conformational of channel protein - opens pore
Pore allows ions to move in and out
Example nicorinic acetylcholine
Acetylcholine and skeletal muscle
Causes muscle contraction
What are chemical messages referred as?
Ligands because they exert an effect on receptors
The ligand GABA binds to receptor ….
And what are the physiological effects of activation
Binds to GABAa and the actions are inhibition of neural activity
Glutamate binds to receptor ….
and what is the action it has
NMDA
Synaptic plasticity and memory formation
The ligand 5-HT binds to receptor ….
What are the physiological effects of that?
5-HT3
And it causes anxiety and emesis
Signal transduction events for G protein coupled receptors
1) 7TM receptor and heterotrimeric G protein are inactive
2) Ligand binding changes conformational of receptor
3)Unassociated G protein binds to receptor on the internal side -> bound GDP molecule is phosphorylated to GTP (GDP exchanged for GTP)
4)G protein dissociates into two active components
α subunit
βγ- subunit
These 2 can act as second messengers
5)Which bind to their target proteins
6)Internal GTPase on alpha subunit dephosphorylates GTP->GDP (GTP is on the alpha subunit)
7)Alpha subunit dissociates from target protein and is inactive again
8)Receptor remains active as long as ligand is bound and can activate further heterotrimeric G-proteins
9) the alpha and beta gamma subunits join again
What does the G protein complex consist of?
An alpha subunit, beta gamma subunit and associated GDP
Also called 7 transmembrane receptors because you need to cross the membrane 7 times
What is the AT-1 G subunit, ligand and physiological effect
Gαq
Angiotensin II
Blood vessels, vasoconstriction and increased blood pressure
What is the subunit of M3 muscarinic, ligand and effect ?
Gαq
Acetycholine
Bronchi, bronchoconstriction, decreased air flow
What is the subunit, ligand and effect of the β1 adrenergic receptor
Gαs
NE, Ad
Heart - increased heart rate, increased force of contraction
Subunit, ligand and effect of the D1 dopaminergic receptor
Gαs
Dopamine
Neurones - increase neuronal growth
What is the subunit, ligand and effect of the α2 adrenergic receptor
Gαi
NE Ad
Blood vessels - vasodilation, decreased blood pressure
What is the subunit, ligand and effect of the M2 muscarinic receptor
Gαi
Acetylcholine
Heart decreased heart rate
What does Gs linked receptor stimulate?
Adenylyl cyclase
Converts ATP to cyclic ATP -> cAMP
cAMP activates protein kinase A PKA
Eg beta 1 adrenergic receptor
What does the Gi protein linked receptor do?
Inhibits adenylyl cyclase
Reduces levels of protein kinase A
M2 muscarinic receptor
What does Gq protein linked receptor do ?
It stimulates phospholipase C PLC
Converts PIP2 to IP3 and DAG
IP3 stimulates calcium ion release
DAG activates PKC
AT -1 angiotensin receptor
How do enzyme linked receptors work?
- ligand binding -> receptor clustering
- receptors clustering
- (cytoplasmic domain) enzymes phosphorylate receptor
- phosphorylation - binding of signalling proteins to cytoplasmic domain
- these signalling proteins recruit other signalling proteins, signal is generated within the cell
What are enzyme linked receptors?
They have a transmembrane domain which has a ligand binding domain on the outside and specialised enzymes on the inside
Can enzyme linked receptors work by themselves?
No dont work alone, they need one receptor protein to activate the intracellular enzyme!
What is the enzyme, ligand and effect of the Insulin CD220 receptor?
Tyrosine kinase
Insulin
Glucose uptake and lipid metabolism
What is the enzyme, ligand, effect of the NPR1 receptor?
GC enzyme
ANP & BNP
Vasodilation and reduction in blood pressure
What is the enzyme, ligand and effect of the TGF β1 ( transforming growth factor) ?
Serine/ threonine kinase
TGF β
Apoptosis
