Synaptotagmin IV: A Multifunctional Regulator of Peptidergic Nerve Terminals

Many members of the synaptotagmin (Syt) protein family bind Ca(2+) and trigger exocytosis, but some Syts appear to have no Ca(2+)-dependent actions and their biological functions remain obscure. Syt IV is an activity-induced brain protein with no known Ca(2+)-dependent interactions; its sub-cellular localization and biological functions have sparked considerable controversy. This study reports the presence of Syt IV on both dense-core and microvesicles in posterior pituitary nerve terminals. In terminals from Syt IV knock-out mice compared to wild-type, low Ca(2+) entry triggered more exocytosis, high Ca(2+) entry triggered less exocytosis, and endocytosis was accelerated. Dense-core and microvesicle fusion was enhanced in cell-attached patches, and dense-core vesicle fusion pores had conductances half as large as in wild-type. Given the neuroendocrine functions of the posterior pituitary, changes in Syt IV levels could play roles in endocrine transitions involving alterations in release of the neuropeptides oxytocin and vasopressin.