TRIM9 Controls Growth Cone Responses to Netrin Through DCC and UNC5C.

ABSTRACT: The guidance cue netrin-1 promotes both growth cone attraction and growth cone repulsion. How netrin-1 elicits diverse axonal responses, beyond engaging the netrin receptor DCC and UNC5 family members, remains elusive. Here, we demonstrate that murine netrin-1 induces biphasic axonal responses in cortical neurons: Attraction at lower concentrations and repulsion at higher concentrations using both a microfluidic-based netrin-1 gradient and bath application of netrin-1. We find that repulsive turning in a netrin gradient is blocked by knockdown of UNC5C, whereas attractive turning is impaired by knockdown of DCC. TRIM9 is a brain-enriched E3 ubiquitin ligase previously shown to bind and cluster the attractive receptor DCC at the plasma membrane and regulate netrin-dependent attractive respo

SUBMITTER: Mutalik SP 

PROVIDER: S-EPMC11834693 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature