Abstract
SUMMARYMany members of the synaptotagmin (Syt) protein family bind Ca2+ and trigger exocytosis, but some Syts appear to have no Ca2+-dependent actions and their biological functions remain obscure. Syt IV is an activity-induced brain protein with no known Ca2+-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 Ca2+ entry triggered more exocytosis, high Ca2+ 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.
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