A Nedd4 E3 Ubiquitin Ligase Pathway Inhibits Robo1 Repulsion and Promotes Commissural Axon Guidance across the Midline.

ABSTRACT: Commissural axons initially respond to attractive signals at the midline, but once they cross, they become sensitive to repulsive cues. In insects and mammals, negative regulation of the surface expression of Roundabout (Robo) receptors prevents premature response to Slit. We previously identified two mammalian Nedd4 interacting proteins, Ndfip1 and Ndfip2, that act analogously to Drosophila Commissureless (Comm) to recruit mammalian Robo1 to late endosomes. However, whether Nedd4 E3 ubiquitin ligases are required for Ndfip-mediated Robo1 regulation and midline axon crossing in vivo is not known. Here, we show using in vitro biochemical techniques and genetic analysis using embryonic mice of either sex that Nedd4-1 and Nedd4-2 are specifically required for Robo1 regula

SUBMITTER: Gorla M 

PROVIDER: S-EPMC9546450 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature