TRIM67 Regulates Exocytic Mode and Neuronal Morphogenesis via SNAP47

Neuronal morphogenesis involves dramatic plasma membrane expansion, likely fueled by SNARE-mediated exocytosis. Distinct fusion modes described at neuronal synapses include full-vesicle-fusion (FVF) and kiss-and-run fusion (KNR). During FVF, lumenal cargo is secreted and vesicle membrane incorporates into the plasma membrane. During KNR a transient fusion pore secretes cargo, but closes without membrane addition. In contrast, fusion modes are not described in developing neurons where plasma membrane expansion is significant. Here, we resolve individual exocytic events in developing murine cortical neurons and use new classification tools to identify four distinguishable fusion modes: two FVF-like modes that insert membrane material and two KNR-like modes that do not. Discrete fluorescence profiles suggest distinct behavior of the fusion pore with each mode. Simulations and experiments agree that FVF-like exocytosis provides sufficient membrane material for morphogenesis. We find the E3 ubiquitin ligase TRIM67 promotes FVF-like exocytosis. Our data suggest this is accomplished in part by limiting incorporation of the Qb/Qc SNARE SNAP47 into SNARE complexes and thus, SNAP47 involvement in exocytosis.