Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Membrane Fusion: Grappling with SNARE and SM Proteins
Thomas C. Südhof1 and
James E. Rothman2
The two universally required components of the intracellularmembrane fusion machinery, SNARE and SM (Sec1/Munc18-like) proteins,play complementary roles in fusion. Vesicular and target membrane–localizedSNARE proteins zipper up into an -helical bundle that pullsthe two membranes tightly together to exert the force requiredfor fusion. SM proteins, shaped like clasps, bind to trans-SNAREcomplexes to direct their fusogenic action. Individual fusionreactions are executed by distinct combinations of SNARE andSM proteins to ensure specificity, and are controlled by regulatorsthat embed the SM-SNARE fusion machinery into a physiologicalcontext. This regulation is spectacularly apparent in the exquisitespeed and precision of synaptic exocytosis, where synaptotagmin(the calcium-ion sensor for fusion) cooperates with complexin(the clamp activator) to control the precisely timed releaseof neurotransmitters that initiates synaptic transmission andunderlies brain function.
1 Department of Cellular and Molecular Physiology, Stanford University, Palo Alto, CA 94304, USA. E-mail: tcs1{at}stanford.edu 2 Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. E-mail: james.rothman{at}yale.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
REPORTS
Claudio G. Giraudo, Alejandro Garcia-Diaz, William S. Eng, Yuhang Chen, Wayne A. Hendrickson, Thomas J. Melia, and James E. Rothman (23 January 2009) Science323 (5913), 512.
[DOI: 10.1126/science.1166500] |Abstract »|Full Text »|PDF »|Supporting Online Material »
M. T. Harper and A. W. Poole (2009)
Blood
114, 489-491
|Full Text »|PDF »
{alpha}-Latrotoxin Stimulates a Novel Pathway of Ca2+-Dependent Synaptic Exocytosis Independent of the Classical Synaptic Fusion Machinery.
F. Deak, X. Liu, M. Khvotchev, G. Li, E. T. Kavalali, S. Sugita, and T. C. Sudhof (2009)
J. Neurosci.
29, 8639-8648
|Abstract »|Full Text »|PDF »
Complexin-I Is Required for High-Fidelity Transmission at the Endbulb of Held Auditory Synapse.
N. Strenzke, S. Chanda, C. Kopp-Scheinpflug, D. Khimich, K. Reim, A. V. Bulankina, A. Neef, F. Wolf, N. Brose, M. A. Xu-Friedman, et al. (2009)
J. Neurosci.
29, 7991-8004
|Abstract »|Full Text »|PDF »
Newcomer insulin secretory granules as a highly calcium-sensitive pool.
-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. 
