The juxtamembrane linker of synaptotagmin 1 regulates Ca²⁺ binding via liquid-liquid phase separation.

ABSTRACT: Synaptotagmin (syt) 1, a Ca²⁺ sensor for synaptic vesicle exocytosis, functions in vivo as a multimer. Syt1 senses Ca²⁺ 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). Interestingly, condensate formation negatively regulates the Ca²⁺-sensitivity of syt1. Moreover, Ca²⁺ and anionic phospholipids facilitate the observed phase separation, and increases in [Ca²⁺]_i promote the fusion of syt1 droplets in living cells. Together, these observations suggest a condensate-mediated feedback loop that se

SUBMITTER: Mehta N 

PROVIDER: S-EPMC10441399 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature