Proteolytic cleavage of Slit by the Tolkin protease converts an axon repulsion cue to an axon growth cue in vivo.

ABSTRACT: Slit is a secreted protein that has a canonical function of repelling growing axons from the CNS midline. The full-length Slit (Slit-FL) is cleaved into Slit-N and Slit-C fragments, which have potentially distinct functions via different receptors. Here, we report that the BMP-1/Tolloid family metalloprotease Tolkin (Tok) is responsible for Slit proteolysis in vivo and in vitro. In Drosophila tok mutants lacking Slit cleavage, midline repulsion of axons occurs normally, confirming that Slit-FL is sufficient to repel axons. However, longitudinal axon guidance is highly disrupted in tok mutants and can be rescued by midline expression of Slit-N, suggesting that Slit is the primary substrate for Tok in the embryonic CNS. Transgenic restoration of Slit-N or S

SUBMITTER: Kellermeyer R 

PROVIDER: S-EPMC7648596 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature