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

Rhea van de Bospoort, Margherita Farina, Sabine K Schmitz, Arthur de Jong, Heidi de Wit, Matthijs Verhage, Ruud F Toonen

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)883-91
Number of pages9
JournalJournal of Cell Biology
Issue number6
Publication statusPublished - 10 Dec 2012
Externally publishedYes


  • Animals
  • Cells, Cultured
  • Female
  • Hippocampus/physiology
  • Intracellular Signaling Peptides and Proteins/biosynthesis
  • Male
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins/biosynthesis
  • Neurons/physiology
  • Presynaptic Terminals/physiology
  • Secretory Vesicles/secretion


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