Endolysosomal TPCs regulate social behavior by controlling oxytocin secretion.

ABSTRACT: Oxytocin (OT) is a prominent regulator of many aspects of mammalian social behavior and stored in large dense-cored vesicles (LDCVs) in hypothalamic neurons. It is released in response to activity-dependent Ca²⁺ influx, but is also dependent on Ca²⁺ release from intracellular stores, which primes LDCVs for exocytosis. Despite its importance, critical aspects of the Ca²⁺-dependent mechanisms of its secretion remain to be identified. Here we show that lysosomes surround dendritic LDCVs, and that the direct activation of endolysosomal two-pore channels (TPCs) provides the critical Ca²⁺ signals to prime OT release by increasing the releasable LDCV pool without directly stimulating exocytosis. We observed a dramatic reduction in plasma OT levels in TP

SUBMITTER: Martucci LL 

PROVIDER: S-EPMC9963339 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature