Mech of neurotransmitter release

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Mech of neurotransmitter release
2013-01-13 05:24:42
MODA SNARE neurotransmitter release

mech of neurotransmitter release
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  1. Visualising nerve junctions
    Make fluorescent derivative of NA with hot formaldehyde vapour
  2. Describe SNAREs
    • Synaptobrevin: v-SNARE, anchored in vesicle membrane by a hydrophobic carboxy terminus. central 70aa alpha-helix
    • Syntaxin: t-SNARE
    • SNAP 25: t-SNARE
    • Core complex: 4 a-helices (1 each, 2 from SNAP 25)
    • form a leucine zipper -> brings vesicle and plasma membranes close together
  3. Botulinum toxin
    • Cleaves target SNARE by peptidase activity
    • Specific SNARE depends on which of 7 subtypes
    • B, D, F, G: Synaptobrevin
    • A, E: SNAP-25
    • C1: Syntaxin and SNAP-25
    • Insertion into cholinergic neurons: C-terminus of heavy chain binds nucleoside receptor eg GT1b, N terminus translocates light chain in through channel
    • Botulinum anti-toxin only works within 30mins of adsorption of toxin
    • Symptoms: somatic muscle weakness (inc resp), loss of cholinergic activity (constipation, blurred vision, dry skin, urinary retention), slowed heart rate (due to effects on NA nerves?)
  4. Tetanus toxin
    • Binds to synaptobrevin
    • Retrogradely transported to cell body, then transferred to inhibitory interneuron - this cannot now release its transmitter, so the motor neuron becomes excitable
  5. Synaptotagmin
    • Calcium sensor
    • N-terminal TM region in vesicle
    • 2 low affinity Ca binding regions (homology to PKC)
    • binds to phospholipids (inc syntaxin) in Ca dependent manner
  6. Synapsins
    • Non-phosphorylated: bound to vesicles and cytoskeleton
    • Phosphorylated (by PKA and CaM kinase II): dissociate from vesicle: vesicle can translocate to active zone