In the late 1990s, he and Reinhard Jahn, now at the Max Planck Institute of Biophysical Chemistry, determined the structures of some of the key proteins and complexes involved in the process of
synaptic vesicle fusion.
Beginning in 1988 Scheller, then at Stanford, succeeded in characterizing several key proteins necessary for
synaptic vesicle fusion with the presynaptic membrane, the prerequisite step for neurotransmitter release.
During this time, we together with our long - time collaborators Reinhard Jahn and Jose Rizo, and in parallel with Richard Scheller and others, discovered the role of SNARE and SM proteins in
synaptic vesicle fusion.
We generated knockout mice lacking synaptobrevin / VAMP 2, the vesicular SNARE protein responsible for
synaptic vesicle fusion in forebrain synapses, to make use of the exquisite temporal resolution of electrophysiology in measuring fusion.
During
synaptic vesicle fusion, the soluble N - ethylmaleimide - sensitive factor — attachment protein receptor (SNARE) protein syntaxin - 1 exhibits two conformations that both bind to Munc18 - 1: a «closed» conformation outside the SNARE complex and an «open» conformation in the SNARE complex.
Thus, the closed conformation of syntaxin - 1 gates the initiation of
the synaptic vesicle fusion reaction, which is then mediated by SNARE - complex / Munc18 -1 assemblies.
Not exact matches
The
synaptic vesicle protein that mediates membrane
fusion during exocytosis also regulates the rate and extent of this process by controlling
vesicle tethering.
Toxins that cleave three different subunits of the vesicular
fusion machinery reveal the detailed kinetics of
synaptic vesicle release.
Voltage-gated calcium channels can not form properly when cacophony is mutated, preventing
fusion of the
synaptic vesicle with the plasma membrane and neurotransmitter release.
Before the
fusion of
synaptic vesicles with the plasma membrane, a protein complex is thought to form between VAMP — an integral membrane protein of the
vesicle — and two proteins associated with the plasma membrane, SNAP - 25 and syntaxin.
Because the two molecules bound to one another Scheller proposed that VAMP, the
synaptic vesicle protein, bridges to syntaxin, the plasma membrane protein — thereby providing a scaffold onto which the molecular machinery that catalyzes membrane
fusion can be assembled.
Mobilization and
fusion of a non-recycling pool of
synaptic vesicles under conditions of endocytic blockade.
Richard Scheller has used a combination of biochemistry, molecular biology, and cell biology to identify several key
synaptic vesicle and plasma membrane proteins involved in
fusion of the neurotransmitter - containing
vesicles with the membrane of the presynaptic terminal.
During an action potential, calcium influx into the presynaptic terminal triggers the
fusion of
synaptic vesicles with the plasma membrane, leading to the release of transmitter through the process of exocytosis.