Chapman Lab

University of Wisconsin-Madison

NEUROSCIENCES

Madison · United States

NIH-funded
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NIH R01 · 2024

Synaptotagmin C2B Domain as a Ca2+ Sensing Module

Project Summary/Abstract In this competitive renewal, we continue our studies of synaptotagmin (syt) isoforms that regulate the release of neurotransmitters and hormones. The founding member of this gene family, syt1, was discovered in 1981 and has been shown to function as the major Ca2+ sensor for synchronous synaptic vesicle (SV) exocytosis in neurons. Surprisingly, the most fundamental property of syt1—it's ability to bind and become activated by Ca2+—remains one of its least understood properties. Syt1 senses Ca2+ via tandem C2 domains, C2A and C2B, and five acidic Ca2+ binding residues have been proposed to coordinate 2-3 Ca2+ ions per domain. However, substitution of these residues…

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