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