SNAREs at the Synapse

Using tiny lipid discs, scientists resolve contradictory evidence about how many proteins are required for neurotransmitter release.

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There is very little about membrane vesicle fusion that Yale University biochemist James Rothman doesn’t know—he codiscovered SNAREs, the proteins that orchestrate the process. But one unanswered question in the field of membrane fusion has been what happens during the first milliseconds of synaptic transmission between neurons—when a vesicle full of neurotransmitters inside a neuron fuses to the cell membrane, opening a pore to release its contents into the synapse.

A fusion pore, the opening that occurs when a vesicle binds to a cell membrane, is present for just hundreds of microseconds, a thousand times shorter than the blink of an eye. Immediately after it opens, the pore rapidly expands as the vesicle membrane melts into the surrounding cell membrane. That quick transition has made it extremely difficult to study the pore, says Rothman. “We thought that if we could find a way to artificially stabilize the fusion pore, without ...

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