Membrane fusion: grappling with SNARE and SM proteins.
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.
Südhof
Thomas C
TC
Department of Cellular and Molecular Physiology, Stanford University, Palo Alto, CA 94304, USA. tcs1@stanford.edu
Rothman
James E
JE
D020816:Amino Acid Motifs; D000818:Animals; D008561:Membrane Fusion; D051938:Munc18 Proteins / Q000737:chemistry / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D050765:Qa-SNARE Proteins / Q000737:chemistry / Q000378:metabolism; D050600:SNARE Proteins / Q000737:chemistry / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000502:physiology; D050857:Synaptotagmins / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000378:metabolism*
D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D050857:Synaptotagmins