Regulated SNARE Folding and Assembly

The membrane fusion machinery contains SNARE proteins, Sec1/Munc18 (SM) proteins, synaptotagmin, complexin, NSF, SNAP, and Munc13. Among these proteins, SNAREs are key players. They couple their dynamical assembly and disassembly to membrane fusion in a precisely controlled manner. Specifically, SNARE assembly generates force to draw two membranes into proximity and use their folding energy to lower the energy barrier of membrane fusion. SM proteins, synaptotagmin, and complexin regulate SNARE assembly and enable membrane fusion to occur at right time and location. After membrane fusion, NSF and SNAP disassemble the fully assembled SNARE complexes in an ATP-dependent manner, recycling SNAREs for next round of fusion. We plan to understand how the above mentioned proteins work together to control exocytosis and how malfunctions of the fusion machinery cause diseases.

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* Co-corresponding authors.