Phosphorylation of Doc2 by EphB2 modulates Munc13-mediated SNARE complex assembly and neurotransmitter release

Abstract At the synapse, presynaptic neurotransmitter release is tightly controlled by release machinery, involving the soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) proteins and Munc13. The Ca2+ sensor Doc2 cooperates with Munc13 to regulate neurotransmitter release, but the underlying mechanisms remain unclear. In our study, we have characterized the binding mode between Doc2 and Munc13 and found that Doc2 originally occludes Munc13 to inhibit SNARE complex assembly. Moreover, our investigation unveiled that EphB2, a presynaptic adhesion molecule (SAM) with inherent