Complexin controls the force transfer from SNARE complexes to membranes in fusion.
Trans-SNAP receptor (SNARE, where SNAP is defined as soluble NSF attachment protein, and NSF is defined as N-ethylmaleimide-sensitive factor) complexes catalyze synaptic vesicle fusion and bind complexin, but the function of complexin binding to SNARE complexes remains unclear. Here we show that in neuronal synapses, complexin simultaneously suppressed spontaneous fusion and activated fast calcium ion-evoked fusion. The dual function of complexin required SNARE binding and also involved distinct amino-terminal sequences of complexin that localize to the point where trans-SNARE complexes insert into the fusing membranes, suggesting that complexin controls the force that trans-SNARE complexes apply onto the fusing membranes. Consistent with this hypothesis, a mutation in the membrane insertion sequence of the v-SNARE synaptobrevin/vesicle-associated membrane protein (VAMP) phenocopied the complexin loss-of-function state without impairing complexin binding to SNARE complexes. Thus, complexin probably activates and clamps the force transfer from assembled trans-SNARE complexes onto fusing membranes.
Maximov
Anton
A
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Tang
Jiong
J
Yang
Xiaofei
X
Pang
Zhiping P
ZP
Südhof
Thomas C
TC
D000200:Action Potentials; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials; D008561:Membrane Fusion; D051379:Mice; D018345:Mice, Knockout; D050505:Mutant Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D011485:Protein Binding; D050683:R-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D050600:SNARE Proteins / Q000737:chemistry / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology; D050857:Synaptotagmins / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; C095992:complexin I; C095993:complexin II; D050857:Synaptotagmins; D002118:Calcium