Conformational Switch of Syntaxin-1 Controls Synaptic Vesicle Fusion

The SNARE protein exists in two conformations during synaptic vesicle fusion, both of which can bind to -1: the "open" conformation in the SNARE complex and a "closed" conformation outside the SNARE complex.

SNARE complexes containing open and -1 are essential for exocytosis. A research team from the USA, Germany and the Netherlands generated knockin/knockout mice that expressed only open syntaxin-1B.

Syntaxin-1Bopen mice were viable at first, but died of generalised seizures at the age of 2 – 3 months. Binding of -1 to was observed to be inhibited in syntaxin-1Bopen synapses, and the size of the readily releasable vesicle pool was smaller. The rate of synaptic vesicle fusion, on the other hand, was extraordinarily increased.

The closed conformation of therefore seems to block the initiation of the synaptic vesicle fusion reaction, which is then mediated by SNARE-complex/-1 assemblies.

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