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• W4385783275 abstract "Abstract Synaptotagmin (syt) 1, a Ca 2+ sensor for synaptic vesicle exocytosis, is thought to act in vivo as a multimer. It senses Ca 2+ via tandem C2-domains that are connected to a single transmembrane domain via a juxtamembrane linker. Here, we show that this linker segment harbors a lysine-rich, intrinsically disordered region that is necessary and sufficient to mediate liquid-liquid phase separation (LLPS). Unexpectedly, these interactions negatively regulate the Ca 2+ -sensitivity of the tandem C2-domains of syt1. Ca 2+ and anionic phospholipids promote the observed phase separation. This potentially creates a feedback loop that might serve to finetune the ability of syt1 to trigger release, via alterations in Ca 2+ binding activity and potentially through the impact of LLPS on membrane curvature during fusion reactions. In summary, the juxtamembrane linker of syt1 emerges as a regulator of syt1 function by driving self-association via LLPS." @default.
• W4385783275 created "2023-08-13" @default.
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• W4385783275 date "2023-08-12" @default.
• W4385783275 modified "2023-10-18" @default.
• W4385783275 title "The juxtamembrane linker of synaptotagmin 1 regulates Ca²⁺binding via liquid-liquid phase separation" @default.
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• W4385783275 doi "https://doi.org/10.1101/2023.08.11.551903" @default.
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