| First Author | Winkle CC | Year | 2014 |
| Journal | J Cell Biol | Volume | 205 |
| Issue | 2 | Pages | 217-32 |
| PubMed ID | 24778312 | Mgi Jnum | J:215804 |
| Mgi Id | MGI:5606264 | Doi | 10.1083/jcb.201311003 |
| Citation | Winkle CC, et al. (2014) A novel Netrin-1-sensitive mechanism promotes local SNARE-mediated exocytosis during axon branching. J Cell Biol 205(2):217-32 |
| abstractText | Developmental axon branching dramatically increases synaptic capacity and neuronal surface area. Netrin-1 promotes branching and synaptogenesis, but the mechanism by which Netrin-1 stimulates plasma membrane expansion is unknown. We demonstrate that SNARE-mediated exocytosis is a prerequisite for axon branching and identify the E3 ubiquitin ligase TRIM9 as a critical catalytic link between Netrin-1 and exocytic SNARE machinery in murine cortical neurons. TRIM9 ligase activity promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. We identified a direct interaction between TRIM9 and the Netrin-1 receptor DCC as well as a Netrin-1-sensitive interaction between TRIM9 and the SNARE component SNAP25. The interaction with SNAP25 negatively regulates SNARE-mediated exocytosis and axon branching in the absence of Netrin-1. Deletion of TRIM9 elevated exocytosis in vitro and increased axon branching in vitro and in vivo. Our data provide a novel model for the spatial regulation of axon branching by Netrin-1, in which localized plasma membrane expansion occurs via TRIM9-dependent regulation of SNARE-mediated vesicle fusion. |
