Candidate Regulator Of The Temporal Component Of Neurotransmitter Release ...( In a joint effort the groups of Heinr...)

In a joint effort, the groups of Heinrich Betz from the Max Planck Institute for Brain Research (Frankfurt, Germany) and George Augustine from the Duke University (Durham, NC) have tested the hypothesis that NSF, a ubiquitous protein required for a variety of general membrane fusion and secretion events in eukaryotic cells, is also involved in neurotransmitter release at synapses. Their results, appearing in the February 20 issue of SCIENCE, provide the first hints at molecular events that may control the time course of neurotransmitter release.

Nerve cells release neurotransmitter by allowing transmitter containing organelles, so called synaptic vesicles, to fuse with the neuronal plasma membrane, thus secreting their content. This process has recently been found to share many similarities with general vesicle trafficking events, e.g. protein transport to the cell surface, as employed by cells from yeast to mammals. The major differences are speed - synaptic vesicles can perform secretion within 200 microseconds after arrival of a stimulus - and tight control by calcium levels, which must rise thousandfold to trigger vesicle fusion. Using a combination of molecular biological and physiological techniques, the groups of Betz and Augustine now have found evidence that the speed of transmitter release itself may be controlled, somewhat ironically, by the evolutionarily highly conserved general fusion protein NSF (for N-methylmaleimide sensitive fusion protein). The groups have synthesized NSF-fragments and screened these peptides for their potency to prevent the major activator of NSF, the soluble NSF-attachment protein SNAP, from interacting with NSF in vitro. To elucidate the consequences of perturbed NSF-function for an intact synapse, inhibitory peptides were then injected into the nerve termin
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Contact: George Augustine
georgea@neuro.duke.edu
919-681-6165
Max-Planck-Gesellschaft
20-Feb-1998