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PMID: 19164740 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Membrane fusion: grappling with SNARE and SM proteins.

Science (New York, N.Y.) ·Vol. 323 ·No. 5913 ·2009-01-23 ·Pages 474-7

Südhof TC, Rothman JE

Abstract

The two universally required components of the intracellular membrane fusion machinery, SNARE and SM (Sec1/Munc18-like) proteins, play complementary roles in fusion. Vesicular and target membrane-localized SNARE proteins zipper up into an alpha-helical bundle that pulls the two membranes tightly together to exert the force required for fusion. SM proteins, shaped like clasps, bind to trans-SNARE complexes to direct their fusogenic action. Individual fusion reactions are executed by distinct combinations of SNARE and SM proteins to ensure specificity, and are controlled by regulators that embed the SM-SNARE fusion machinery into a physiological context. This regulation is spectacularly apparent in the exquisite speed and precision of synaptic exocytosis, where synaptotagmin (the calcium-ion sensor for fusion) cooperates with complexin (the clamp activator) to control the precisely timed release of neurotransmitters that initiates synaptic transmission and underlies brain function.

MeSH Terms
Amino Acid Motifs Animals Membrane Fusion Munc18 Proteins/chemistry,metabolism Nerve Tissue Proteins/metabolism Protein Binding Protein Conformation Protein Structure, Quaternary Protein Structure, Tertiary Qa-SNARE Proteins/chemistry,metabolism SNARE Proteins/chemistry,metabolism Synapses/physiology Synaptic Transmission Synaptic Vesicles/physiology Synaptotagmins/metabolism Vesicular Transport Proteins/chemistry,metabolism
Chemicals
Munc18 Proteins Nerve Tissue Proteins Qa-SNARE Proteins SNARE Proteins Vesicular Transport Proteins Synaptotagmins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Südhof Thomas C
Department of Cellular and Molecular Physiology, Stanford University, Palo Alto, CA 94304, USA. tcs1@stanford.edu
Rothman James E
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1161748
Email
tcs1@stanford.edu
Published
2009-01-23
Pages
474-7
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3736821
Subset
IM
Grants
NIGMS NIH HHS · R01 GM071458 · United States
Howard Hughes Medical Institute · United States
External Links
PubMed source DOI: 10.1126/science.1161748 PMC Full Text View journal details
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