Munc13 controls the location and efficiency of dense-core vesicle release in neurons

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Munc13 controls the location and efficiency of dense-core vesicle release in neurons

Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In m...

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Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis.

It is currently unknown whether the molecular steps of large dense-core vesicle (LDCV) docking and priming are identical to the corresponding reactions in synaptic vesicle (SV) exocytosis. Munc13s are essential for SV docking and priming, and we systematically analyzed their role in LDCV exocytosis using chromaffin cells lacking individual isoforms. We show that particularly Munc13-2 plays a fu...

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Drosophila CAPS Is an Essential Gene that Regulates Dense-Core Vesicle Release and Synaptic Vesicle Fusion

Calcium-activated protein for secretion (CAPS) is proposed to play an essential role in Ca2+-regulated dense-core vesicle exocytosis in vertebrate neuroendocrine cells. Here we report the cloning, mutation, and characterization of the Drosophila ortholog (dCAPS). Null dCAPS mutants display locomotory deficits and complete embryonic lethality. The mutant NMJ reveals a 50% loss in evoked glutamat...

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Vti1a functions in dense-core vesicle biogenesis

The SNARE-protein Vti1a is proposed to drive fusion of intracellular organelles, but recent data also implicated Vti1a in exocytosis. Here we show that vti1a is absent from mature secretory vesicles in adrenal CCs, but localizes to a compartment near the Trans-Golgi-Network, partially overlapping with Syntaxin6. Exocytosis is impaired in vti1a null cells, partly due to fewer Ca-channels at the ...

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Dense-core vesicle (DCV) exocytosis is a SNARE (soluble N-ethylmaleimide-sensitive fusion attachment protein receptor)-dependent anterograde trafficking pathway that requires multiple proteins for regulation. Several C2 domain-containing proteins are known to regulate Ca2+-dependent DCV exocytosis in neuroendocrine cells. In this study, we identified others by screening all (∼139) human C2 doma...

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ژورنال

عنوان ژورنال: Journal of Cell Biology

سال: 2012

ISSN: 1540-8140,0021-9525

DOI: 10.1083/jcb.201208024