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Membrane fusion at the synapse: Janus faced synaptotagmin-1 helps to keep the fast pace
Date:10/29/2008

d receive information via two structures that make up the synapse. On the sending site, the electrical activity of the neuron needs to be rapidly converted into a chemical signal via release of a hormone or neurotransmitter.

The trigger for this is the flux of calcium ions into the nerve terminal. The receiving neuron on the other site of the synapse detects the neurotransmitter via receptors and converts it again into electrical activity.

It takes no more than 1/1,000th of a second for this to occur. Neuroscientists are not only fascinated by this astonishing speed, but they also recognize that disturbing the speed of synaptic transmission has deleterious consequences on brain function and can lead to various diseases of the nervous system including schizophrenia, depression, Parkinson's disease, epilepsy and Alzheimer's disease.

Rosenmund and colleagues found that synaptotagmin-1 plays an important role in maintaining this speed. Bringing two fusing membranes close enough so that they fuse with each other is a crucial step in the process. The housekeeping machinery that accomplishes this in many biological processes is made up of the so-called SNARE proteins that form protein bundles across vesicle and plasma membranes, hurling the vesicle or balloon-like structure close to the membrane. While this process works very well, it is just too slow for synapses operating in a millisecond.

"That's where synaptotagmin-1 and calcium come into the game," said Rosenmund. "Its C2B domain binds at the top site to calcium ions, allowing the subsequent attachment to of the two membranes."

In their current work, Xue, Rosenmund and colleagues showed that the bottom of the C2B domain is also critical in bringing the membranes of the neuron together with the vesicle's membrane, allowing the release of neurotransmitter.

"Nature invented SNARE first to help the process," said Xue. "But that did not take into account the high dem
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Contact: Glenna Picton
picton@bcm.edu
713-798-4710
Baylor College of Medicine
Source:Eurekalert

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