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


ABSTRACT: 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 munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically.

SUBMITTER: van de Bospoort R 

PROVIDER: S-EPMC3518216 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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

van de Bospoort Rhea R   Farina Margherita M   Schmitz Sabine K SK   de Jong Arthur A   de Wit Heidi H   Verhage Matthijs M   Toonen Ruud F RF  

The Journal of cell biology 20121201 6


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 munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic prefere  ...[more]

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