Synaptotagmin 1 is an Antagonist for Munc18-1 in SNARE-zippering [Membrane Biology]

February 25th, 2015 by Lou, X., Shin, J., Yang, Y., Kim, J., Shin, Y.-K.

In neuroexocytosis, SNAREs and Munc18-1 may consist of the minimal membrane fusion machinery. Consistent with this notion, we observed, using single molecule fluorescence assays, that Munc18-1 stimulates SNARE zippering and SNARE-dependent lipid mixing in the absence of a major Ca2+-sensor synaptotagmin 1 (syt1), providing the structural basis for the conserved function of SM (Sec1/Munc18) proteins in exocytosis. However, when full-length syt1 is present no enhancement of SNARE zippering and no acceleration of Ca2+-triggered content mixing by Munc18-1 are observed. Thus, our results show that syt1 acts as an antagonist for Munc18-1 in SNAREs zippering and fusion pore opening. Although the SM family may serve as part of the fusion machinery in other exocytotic pathways, Munc18-1 may have evolved to play a different role such as regulating syntaxin 1a in neuroexocytosis.