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Martin Lab - How calcium triggers membrane fusion
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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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