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Biochemistry 314: Membrane Fusion



What is the SNARE's role in membrane fusion?

Membrane fusion is (usually) the joining of membranes of cellular transport vesicles with the main cell membrane (or the membrane of a target compartment like a lysosome) in order to complete exocytosis.

A SNARE is a large protein superfamily consisting of more than 60 members in yeast and mammalian cells.
The primary role of SNARE proteins is to pull membranes together.

Complex structure: when formed it is a 4 helix bundle about 120 angstoms across, looks like a coiled coil, zips itself up to pull membranes together. Ca2+ is required (don't know why).

Two categories of snares:
-vesicle or v-SNAREs , which are incorporated into the membranes of transport vesicles during budding
-target or t-SNAREs, which are located in the membranes of target compartments.

budding = forming a new vessicle

In neuromediator release: The core SNARE complex is formed by four α-helices contributed by synaptobrevin, syntaxin and SNAP-25, synaptotagmin serves as a Ca2 + sensor and regulates intimately the SNARE zipping

The best-studied SNAREs are those that mediate docking of synaptic vesicles with the presynaptic membrane. (releasing acetylcholine from vesicles into synaptic cleft) These SNAREs are the targets of the bacterial neurotoxins responsible for botulism and tetanus.

-acronym derived from "soluble NSF attachment receptor"

TETANUS can be caused caused by a botchlinum toxin from bacteria that keeps nerves from firing by preventing the release of the neurotransmitter acetylcholine via exocytosis. Cloistridium tetani. Mild case is called trismus and affects TMJ joint first. Opisthotonus is an extreme case in which all muscles are contracted, person arches back, looks like siezure with no convulsions.

Another way tetanus can be caused is serine protease stopper DIFP, diisopropyl flourophosphate which permanently binds to acetylcholineesterase so the acetylcholine lingers in the synapse & muscle cannot stop contracting. Variations used in nerve gas for which treatment is atropine (not more than 4 x in leg).

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