Cell Signalling Summary - BHCS2004

Cell Signalling Cheat Sheet
3 Main Classes of Ionotropic Receptors

Ligand Receptor Ion Response
Glutamate NMDA Na+ Fast depolarisation
Glutamate KA Na+ Fast depolarisation
Glutamate AMPA Na+ and Slow depolarisation and
Ca+ activation of second
messengers




NMDA

 Magnesium blocks signalling and glycine modulates channel current
 Channel gating may be blocked by agonists like ketamine
 May be excitatory or inhibitory
 2nd messenger activated downstream signalling pathways and post
translational modification by effectors
 Calcium activates calmodium which activates effector proteins



Calcium

 Activates post translational signalling pathways

1. 1st messenger - Glutamate
2. Receptor - NDMA
3. 2nd messenger - Ca2+
4. Effector - CaM
5. Protein Kinase - CaMKII

 This pathway causes phosphorylation of membrane channels
 Channel gating may also result in prolonged changes like
transcriptional mediated changes



G- Protein Coupled Receptors

1. Cell produces signal
2. Binds to GCPR
3. G-protein (Guanine Nucleotide Binding Protein) produces 2nd
messenger

, 4. Activated target protein
5. Transcription, Survival, Protein synthesis



GTPase Regulation

 When on - bound to GTP
 When off - bound to GDP




G-protein Family

 Composed of 3 subunits
 Bring receptors to effectors which catalyses 2nd messenger
o Or bring receptors directly to ion channels
 May be excitatory (N-epinephrine) or inhibitory (Ach)



Trimeric G-Proteins and GTP

1. G-protein inactivate - bound to GDP
2. Recruitment of 7TM - Gains GTP and loses GDP
3. Splits subunits
4. Hydrolyses GTP to GDP - terminating its own activity



G-proteins Couple to 3 Pathways

 Direct effector linked pathway
 Phospholipase C pathway
 Adenyl Cyclase pathway

, Direct Effector Linked Pathway

 Gby subunits directly to effector
 Parasympathetic

1. Ach binds to heart muscle
2. Muscanic Ach receptor
3. G-protein
4. Opens K+
5. Hyperpolarisation
6. Decreased contraction

 Motor Neuron

1. Ach binds to skeletal muscle
2. Nicotinic Ach receptor
3. Ion channel
4. Sodium and calcium flux
5. Depolarisation
6. Increased contraction

Adenyl Cyclase Pathway

 Adenyl Cyclase is an enzyme that catalyses cAMP from ATP
 Pathway

1. Norepinephrine
2. Beta adrenergic
3. G-protein
4. Adenyl Cyclase
5. cAMP
6. Protein kinase A
7. Increased phosphorylation of proteins
8. Increased cardiac contraction



Phospholipase C Pathway

 Phospholipase C is an effector enzyme activated by G-protein
 Pathway
1. Glu
2. mGlu
3. G-protein
4. Phospholipase C
5. Diacyldglycerol or IP3
6. Protein kinase C or Ca2+ release
7. Increased protein phosphorylation and calcium binding
proteins