TY - JOUR TI - CAPS-1 promotes fusion competence of stationary dense-core vesicles in presynaptic terminals of mammalian neurons AU - Farina, Margherita AU - van de Bospoort, Rhea AU - He, Enqi AU - Persoon, Claudia M AU - van Weering, Jan RT AU - Broeke, Jurjen H AU - Verhage, Matthijs AU - Toonen, Ruud F A2 - Brunger, Axel T VL - 4 PY - 2015 DA - 2015/02/26 SP - e05438 C1 - eLife 2015;4:e05438 DO - 10.7554/eLife.05438 UR - https://doi.org/10.7554/eLife.05438 AB - 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. KW - CAPS protein KW - exocytosis KW - neuron KW - dense-core vesicle KW - trafficking JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -