Figure 7. Role of RPH3A in dense core vesicle (DCV) exocytosis.
(A) RPH3A binding to RAB3 through its RAB-binding domain (RBD) ensures confined presynaptic localization of RPH3A. RPH3A binding to SNAP25 through its C2B domain inhibits DCV exocytosis, potentially by inhibiting SNAP25 binding of essential DCV proteins synaptobrevin/VAMP2 and/or synaptotagmin (not depicted). (B) In the absence of RPH3A, DCV exocytosis is not limited. (C) Upon expression of a RPH3A mutant that is unable to bind RAB3A/RAB27A, DCV exocytosis is limited. (D) When RPH3A is unable to bind SNAP25, the SNARE assembly is not restricted and therefore DCV exocytosis is not limited, while RPH3A is still recruited to synapses/release sites via RAB3.