Peripheral neural transmission: Mechanisms of neurotransmitter release Flashcards
Synaptobrevin
v-SNARE
Anchored in the vesicle membrane by a hydrophobic carboxy terminus
Central, 70 aa residue, region forms an alpha helix which complexes with SNAP-25 and syntaxin (associated with the cell membrane) to form the core complex
Core complex
Consists of 4 alpha helices- 1 each from synaptobrevin and syntaxin, 2 from SNAP-25
Helices lie parallel to eachother and form a leucine zipper which brings vesicle & PM close together.
Botulinum toxin
Preferentially acts on cholinergic neurons
C terminus binds to ganglioside “receptor” e.g GT1b
N terminus translocates light chain into cell
Light chain has peptidase activity, cleaves target SNARE
Blocks ACh release- Loss of cholinergic activity.
Muscle weakness, constipation, blurred vision, dry skin etc. HR may be slowed rather than increased due to actions on NA nerves.
Tetanus toxin
Retrogradely transported to cell body of MN
Transfers to inhibitory interneurone & blocks release of transmitter-> MN becomes excitable.
Targets synaptobrevin
Synaptotagmin
Putative Ca2+ sensor
Single TM region at N terminus & 2 sequences with homology to PKC, which can bind several Ca ions with fairly low affinity
C2a domain binds to phospholipids rapidly in a calcium dependent manner
C2b domain binds syntaxin during membrane fusion, and is involved with its dimerisation.
Also involved in recycling of the empty vesicle
Botulinum toxins B, D, F, G
Cleave synaptobrevin
Botulinum toxins A, E
Cleave SNAP-25
Botulinum toxin C1
Cleaves syntaxin and SNAP-25
Synapsins
Anchor vesicles to the cytoskeleton
Phosphorylation (by PKA and Ca2+/ calmodulin- dependent kinase II [CaM kinase II] ) causes them to dissociate from vesicles
Thus when cell activated by increase in intracellular calcium, vesicles are freed to move towards active zone
