Calcium-sensitive synaptotagmin 11-lipid interaction modulates exo-endocytosis.

ABSTRACT: Synaptotagmins (Syts) are the primary Ca²⁺-sensors for synaptic vesicle exocytosis, while most mammalian Syts are non-Ca²⁺-affinitive and play critical roles in neurotransmission and synaptic plasticity with unclear mechanisms. Here, we show that high-alkaline non-Ca²⁺-binding Syt11 exhibits higher affinity for acidic phospholipids and Ca²⁺-inhibited liposome-binding, thereby competing with the Ca²⁺-binding Syt1. Physiological levels of Ca²⁺ eliminate this competition by promoting Ca²⁺-dependent membrane insertion of Syt1 while suppressing Syt11's binding through electrostatic shielding of the membrane surface. Site-directed mutagenesis reveals a dual-regional lipid-binding mode (a lysine-rich motif for Ca^2+<

SUBMITTER: Wu X 

PROVIDER: S-EPMC12819558 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature