Dynamin controls neuropeptide secretion by organizing dense-core vesicle fusion sites.

Here, we identify dynamins, yeast Vps1 orthologs, as important DCV fusion site organizers in mammalian CNS neurons. Genetic or pharmacological inactivation of all three dynamins strongly impaired DCV exocytosis, while SV exocytosis remained unaffected.

Wildtype dynamin restored normal exocytosis, but not GTPase-deficient or membrane-binding mutants that cause neurodevelopmental syndromes. During prolonged stimulation, repeated use of the same DCV fusion location was impaired in dynamin 1-3 triple knockout neurons. The syntaxin-1 staining efficiency, but not its expression level, was reduced. αSNAP expression restored this.