Complexin and Ca2+ stimulate SNARE-mediated membrane fusion.
Ca(2+)-triggered, synchronized synaptic vesicle fusion underlies interneuronal communication. Complexin is a major binding partner of the SNARE complex, the core fusion machinery at the presynapse. The physiological data on complexin, however, have been at odds with each other, making delineation of its molecular function difficult. Here we report direct observation of two-faceted functions of complexin using the single-vesicle fluorescence fusion assay and EPR. We show that complexin I has two opposing effects on trans-SNARE assembly: inhibition of SNARE complex formation and stabilization of assembled SNARE complexes. Of note, SNARE-mediated fusion is markedly stimulated by complexin, and it is further accelerated by two orders of magnitude in response to an externally applied Ca(2+) wave. We suggest that SNARE complexes, complexins and phospholipids collectively form a complex substrate for Ca(2+) and Ca(2+)-sensing fusion effectors in neurotransmitter release.
Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, 1110 West Green Street, Urbana, Illinois 61801-3080, USA.
Tae-Young
TY
Yoon
Xiaobing
X
Lu
Jiajie
J
Diao
Soo-Min
SM
Lee
Taekjip
T
Ha
Yeon-Kyun
YK
Shin
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001681:Biological Assay; D002118:Calcium / Q000494:pharmacology*; D031541:Fluorescence Resonance Energy Transfer; D008561:Membrane Fusion / Q000187:drug effects*; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D050600:SNARE Proteins / Q000378:metabolism*; D053835:Unilamellar Liposomes / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D050600:SNARE Proteins; D053835:Unilamellar Liposomes; C095992:complexin I; D002118:Calcium