Shared receptors in axon guidance: SAX-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function.
The C. elegans SAX-3/Robo receptor acts in anterior-posterior, dorsal-ventral and midline guidance decisions. Here we show that SAX-3 signaling involves the C. elegans Enabled protein UNC-34 and an unexpected Netrin-independent function of the Netrin receptor UNC-40/DCC. Genetic interactions with gain- and loss-of-function mutations suggest that unc-34 and unc-40 act together with sax-3 in several guidance decisions, but the C. elegans Netrin gene unc-6 does not act in the same genetic pathways. Within the migrating axon, sax-3, unc-34 and unc-40 all act cell-autonomously. Our results support a role for UNC-34/Enabled proteins in SAX-3-mediated repulsion, and show that UNC-40/DCC can potentiate SAX-3/Robo signaling via a mechanism that may involve direct binding of the two guidance receptors. A combinatorial logic dictates alternative functions for UNC-40/DCC, which can act in attraction to UNC-6/Netrin, repulsion from Netrin (with UNC-5), or repulsion from Slit (with SAX-3).
Yu
Timothy W
TW
Howard Hughes Medical Institute, Program in Neuroscience, Department of Anatomy and of Biochemistry and Biophysics, The University of California, San Francisco, California 94143, USA.
Hao
Joe C
JC
Lim
Wendell
W
Tessier-Lavigne
Marc
M
Bargmann
Cornelia I
CI
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020439:Growth Cones / Q000502:physiology; D015801:Helminth Proteins / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins; D000075385:Netrins; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D000097905:Roundabout Proteins
D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D015801:Helminth Proteins; D009419:Nerve Tissue Proteins; D000075385:Netrins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C092744:ENA-VASP proteins; C102174:UNC-40 protein, C elegans; C078146:UNC-6 protein, C elegans; C077588:UNC-5 protein, C elegans