TRIM9 Mediates Netrin-1-Induced Neuronal Morphogenesis in the Developing and Adult Hippocampus

Known TRIM9 interactions. A, In the absence of Netrin-1, TRIM9 inhibits SNAP25 in a ligase-independent manner to inhibit exocytosis. TRIM9 also acts as a filopodia “off” switch by ubiquitinating actin polymerase VASP. Ubiquitinated VASP is dissociated from the ends of actin filaments, leading to decreased actin polymerization. B, When Netrin-1 is present, TRIM9 interacts with Netrin-1 receptor DCC in a ligase-dependent manner. TRIM9's interaction with SNAP25 is inhibited upon Netrin-1 introduction, leading to exocytosis-mediated membrane expansion. TRIM9 ubiquitination of VASP is also inhibited, leading to VASP association with actin filaments, increased actin filament polymerization, and promotion of filopodia formation. F-actin, filamentous actin; Ub, ubiquitination.