Wk 4.2 Receptors and signal transduction

Question 1

1. What percentage does the brain weigh?
2. How much oxygen does it consume?
   3.What is most of the energy used in?

Answer 1

1.2% human body mass
2.Consumes approx. 20 %oxygen
3.Most energy used insynaptic transmission

Question 2

How does Signal Transduction work within the Cell

Answer 2

• Activated receptors stimulate specific second messenger production
• These activate other enzymes, which activate other enzymes.
• The cascade continues and amplifys.

Question 3

What are the steps of signal transduction?

Answer 3

1) Signal Molecule (primary messenger) travels to cell

2) Signal binds to receptor, initiates structural change ,transmitted through protein and across membrane

3) Receptors activate signalling proteins

4) Second messengers generated and signal amplified=can diffuse in cell

5) Further signalling proteins activated

6) Signal propagation and amplification* often by phosphorylation

7) Target of signal affected (activation, inhibition, insertion, removal)= other receptors* cytoskeletal proteins* metabolic enzymes* transcription factors

8) Signal terminated= physical removal of signal* Dephosphorylation of proteins

Question 4

What are the outcomes of Signal Transduction?

Answer 4

-Altered protein conformation and structure
- Altered post-translational modification of proteins
-Altered protein location
-Altered rates of gene expressio

Question 5

what is the meaning of ionic tropic, ,metabotropic and neurotransmitter?

Answer 5

*Ionotropic - receptor forms cation channels
* Metabotropic – receptor linked to G-proteins
* Neurotransmitter – L-glutamate

Question 6

What is the structure and function of AMPA

Answer 6

• all subunits alternatively spliced- most subunits RNA edited- 4 genes, potentially

-rapid kinetics, mediate fast synaptic transmission, desensitization & Na+ influx,

Question 7

How does AMPAR work.

Answer 7

1.Glutamate binding opens ion channel; Na+ influx

2. Depolarization of post-synaptic dendrite* AMPAR very rapidly desensitize (channels shut, whilst ligand still bound)

3.AMPA receptors can be phosphorylated by PKC, PKA, CamKII at multiplesites

4. Phosphorylation modulates their channel properties
5. Phosphorylation modifies scaffold protein interactions

6.Phosphorylation /dephosphorylation their affects trafficking at synapses

7. Causes change in AMPAR type and number at synapse

Question 8

What is the ionotropic receptor like?

Answer 8

-Ligand-binding opens a cationchannel through membrane
-Assembled from 4 subunits
-Effects are on the millisecond timescale
-Post-synaptic localisation 3 subunits= NMDA,AMPA and Kainte receptors

Question 9

What is the metabotropic receptor like?

Answer 9

-Ligand-binding activates intracellularG-proteins
-Effects are on seconds to hours timescale (with exceptions
-8 different mGluR are grouped into 3subgroups according to secondmessenger and sequence

Question 10

How does glutamate get in the vesicles

Answer 10

It is synthesised from glutamine, the transmitter gets to the vesicles by the V-ATPase that pumps protons inside the vesicle and the proton gradient imports glutamate inside the vesicle which is then released to the post synaptic

Question 11

How does NMDA work?

Answer 11

-NMDA opens by binding to its ligand to glutamate and glycine which acts as the NMDA receptors
- MG binds to it and acts as a plug by blocking the synaptic current from happening
- Removal of the mg requires depolarisation to be kick out