Inhibition of netrin-mediated axon attraction by a receptor protein tyrosine phosphatase.
During axon guidance, the ventral guidance of the Caenorhabditis elegans anterior ventral microtubule axon is controlled by two cues, the UNC-6/netrin attractant recognized by the UNC-40/DCC receptor and the SLT-1/slit repellent recognized by the SAX-3/robo receptor. We show here that loss-of-function mutations in clr-1 enhance netrin-dependent attraction, suppressing ventral guidance defects in slt-1 mutants. clr-1 encodes a transmembrane receptor protein tyrosine phosphatase (RPTP) that functions in AVM to inhibit signaling through the DCC family receptor UNC-40 and its effector, UNC-34/enabled. The known effects of other RPTPs in axon guidance could result from modulation of guidance receptors like UNC-40/DCC.
Chang
Chieh
C
Department of Biological Sciences, Howard Hughes Medical Institute (HHMI), Stanford University, Stanford, CA 94305, USA.
Yu
Timothy W
TW
Bargmann
Cornelia I
CI
Tessier-Lavigne
Marc
M
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D003463:Cues; D017238:Genes, Helminth; D008870:Microtubules / Q000502:physiology / Q000648:ultrastructure; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000075385:Netrins; D016366:Open Reading Frames; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D054557:Receptor-Like Protein Tyrosine Phosphatases; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction; D000097905:Roundabout Proteins
D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D009419:Nerve Tissue Proteins; D000075385:Netrins; D017027:Protein Tyrosine Phosphatases; D054557:Receptor-Like Protein Tyrosine Phosphatases; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C102174:UNC-40 protein, C elegans; C078146:UNC-6 protein, C elegans; C112492:CLR-1 protein, C elegans