title: CAPS-1 promotes fusion competence of stationary dense-core vesicles in presynaptic terminals of mammalian neurons.
abstract: Neuropeptides released from dense-core vesicles (DCVs) modulate neuronal activity, but the molecules driving DCV secretion in mammalian neurons are largely unknown. We studied the role of calcium-activator protein for secretion (CAPS) proteins in neuronal DCV secretion at single vesicle resolution. Endogenous CAPS-1 co-localized with synaptic markers but was not enriched at every synapse. Deletion of CAPS-1 and CAPS-2 did not affect DCV biogenesis, loading, transport or docking, but DCV secretion was reduced by 70% in CAPS-1/CAPS-2 double null mutant (DKO) neurons and remaining fusion events required prolonged stimulation. CAPS deletion specifically reduced secretion of stationary DCVs. CAPS-1-EYFP expression in DKO neurons restored DCV secretion, but CAPS-1-EYFP and DCVs rarely traveled together. Synaptic localization of CAPS-1-EYFP in DKO neurons was calcium dependent and DCV fusion probability correlated with synaptic CAPS-1-EYFP expression. These data indicate that CAPS-1 promotes fusion competence of immobile (tethered) DCVs in presynaptic terminals and that CAPS-1 localization to DCVs is probably not essential for this role.
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, Amsterdam, Netherlands.
authors.forename: Margherita
authors.initials: M
authors.lastname: Farina
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, Amsterdam, Netherlands.
authors.forename: Rhea
authors.initials: R
authors.lastname: van de Bospoort
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, Amsterdam, Netherlands.
authors.forename: Enqi
authors.initials: E
authors.lastname: He
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Persoon
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Jan R T
authors.initials: JR
authors.lastname: van Weering
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Jurjen H
authors.initials: JH
authors.lastname: Broeke
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, Amsterdam, Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, Amsterdam, Netherlands.
authors.forename: Ruud F
authors.initials: RF
authors.lastname: Toonen
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: C510820:Cadps protein, mouse; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins
keywords: CAPS protein; dense-core vesicle; exocytosis; mouse; neurons; neuroscience; trafficking