The slit receptor EVA-1 coactivates a SAX-3/Robo mediated guidance signal in C. elegans.
The SAX-3/roundabout (Robo) receptor has SLT-1/Slit-dependent and -independent functions in guiding cell and axon migrations. We identified enhancer of ventral-axon guidance defects of unc-40 mutants (EVA-1) as a Caenorhabditis elegans transmembrane receptor for SLT-1. EVA-1 has two predicted galactose-binding ectodomains, acts cell-autonomously for SLT-1/Slit-dependent axon migration functions of SAX-3/Robo, binds to SLT-1 and SAX-3, colocalizes with SAX-3 on cells, and provides cell specificity to the activation of SAX-3 signaling by SLT-1. Double mutants of eva-1 or slt-1 with sax-3 mutations suggest that SAX-3 can (when slt-1 or eva-1 function is reduced) inhibit a parallel-acting guidance mechanism, which involves UNC-40/deleted in colorectal cancer.
Fujisawa
Kazuko
K
Samuel Lunenfeld Research Institute of Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
Wrana
Jeffrey L
JL
Culotti
Joseph G
JG
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D003001:Cloning, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009420:Nervous System / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D000097905:Roundabout Proteins
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D000097905:Roundabout Proteins; C523438:EVA-1 protein, C elegans; C492285:slt-1 protein, C elegans