TY - JOUR
T1 - The membrane fusion enigma
T2 - SNAREs, Sec1/Munc18 proteins, and their accomplices guilty as charged?
AU - Rizo-Rey, Jose
AU - Südhof, Thomas C.
PY - 2012
Y1 - 2012
N2 - 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 Ca{}2+{/} and RIM proteins, among others.
AB - 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 Ca{}2+{/} and RIM proteins, among others.
KW - active zone
KW - molecular chaperones
KW - neurotransmitter release
KW - presynaptic plasticity
KW - synaptic vesicle exocytosis
UR - http://www.scopus.com/inward/record.url?scp=84870232182&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870232182&partnerID=8YFLogxK
U2 - 10.1146/annurev-cellbio-101011-155818
DO - 10.1146/annurev-cellbio-101011-155818
M3 - Article
C2 - 23057743
AN - SCOPUS:84870232182
SN - 1081-0706
VL - 28
SP - 279
EP - 308
JO - Annual Review of Cell and Developmental Biology
JF - Annual Review of Cell and Developmental Biology
ER -