The membrane fusion enigma: SNAREs, Sec1/Munc18 proteins, and their accomplices—guilty as charged?

J Rizo, TC Südhof - Annual review of cell and developmental …, 2012 - annualreviews.org
J Rizo, TC Südhof
Annual review of cell and developmental biology, 2012annualreviews.org
Neurotransmitter release is governed by proteins that have homo-logs in most types of
intracellular membrane fusion, including the Sec1/Munc18 protein Munc18-1 and the
SNARE proteins syntaxin-1, synaptobrevin/VAMP, and SNAP-25. The SNAREs initiate
fusion by forming tight SNARE complexes that bring the vesicle and plasma membranes
together. SNARE maintenance in a functional state depends on two chaperone systems
(Hsc70/αCSP/SGT and synuclein); defects in these systems lead to neurodegeneration …
Neurotransmitter release is governed by proteins that have homo-logs in most types of intracellular membrane fusion, including the Sec1/Munc18 protein Munc18-1 and the SNARE proteins syntaxin-1, synaptobrevin/VAMP, and SNAP-25. The SNAREs initiate fusion by forming tight SNARE complexes that bring the vesicle and plasma membranes together. SNARE maintenance in a functional state depends on two chaperone systems (Hsc70/αCSP/SGT and synuclein); defects in these systems lead to neurodegeneration. Munc18-1 binds to an autoinhibitory closed conformation of syntaxin-1, gating formation of SNARE complexes, and also binds to SNARE complexes, which likely underlies the crucial function of Munc18-1 in membrane fusion by an as-yet unclear mechanism. Syntaxin-1 opening is mediated by Munc13s through their MUN domain, which is homologous to diverse tethering factors and may also have a general role in fusion. MUN domain activity is likely modulated in diverse presynaptic plasticity processes that depend on Ca2+ and RIM proteins, among others.
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