Lora L Martucci, Jean-Marie Launay, Natsuko Kawakami, Cécile Sicard, Nathalie Desvignes, Mbarka Dakouane-Giudicelli, Barbara Spix, Maude Têtu, Franck-Olivier Gilmaire, Sloane Paulcan, Jacques Callebert, Cyrille Vaillend, Franz Bracher, Christian Grimm, Philippe Fossier, Sabine de la Porte, Hirotaka Sakamoto, John Morris, Antony Galione, Sylvie Granon, José-Manuel Cancela
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...
February 14, 2023: Proceedings of the National Academy of Sciences of the United States of America