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Martin Lab - How calcium triggers membrane fusion
Calcium is the primary signal in neurons and endocrine cells that triggers membrane fusion for vesicular release of neurotransmitters and peptide hormones. Synaptotagmin proteins (blue) tethered to secretory vesicles are the calcium sensors for regulated secretion. Membrane fusion is executed by SNARE proteins (green) that reside on both membranes and form complexes in trans. Calcium binds synaptotagmin, which drives its interaction with SNAREs. Our recent studies identified two basic patches on the first C2 domain in synaptotagmin that functions as a calcium-dependent switch to mediate interactions with the SNARE proteins. Neuroendocrine cells harboring synaptotagmin mutants with a defective switch were incapable of calcium-triggered secretion.  This work provided direct support for a model in which calcium-bound synaptotagmin interacts with SNAREs to trigger fusion, and provided insight on structural features of synaptotagmin that allow calcium coupling to membrane fusion.

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