Affiliation:
1. Deptartment of Biology/MS 314, University of Nevada, 1664 N. Virginia St., Reno, NV 89557, USA
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 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 Slit-C does repel axons in Slit-null animals. Slit-FL and Slit-N are both biologically active cues with distinct axon guidance functions in vivo. Slit signaling is used in diverse biological processes, thus differentiating between Slit-FL and Slit fragments will be essential for evaluating Slit function in broader contexts.
Funder
National Institutes of Health
Division of Integrative Organismal Systems
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Cited by
5 articles.
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