Abstract
Netrins promote axon outgrowth and turning through DCC/UNC-40 receptors. To characterize Netrin signaling, we generated a gain-of-function UNC-40 molecule, MYR::UNC-40. MYR::UNC-40 causes axon guidance defects, excess axon branching, and excessive axon and cell body outgrowth. These defects are suppressed by loss-of-function mutations in ced-10 (a Rac GTPase), unc-34 (an Enabled homolog), and unc-115 (a putative actin binding protein). ced-10, unc-34, and unc-115 also function in endogenous unc-40 signaling. Our results indicate that Enabled functions in axonal attraction as well as axon repulsion. UNC-40 has two conserved cytoplasmic motifs that mediate distinct downstream pathways: CED-10, UNC-115, and the UNC-40 P2 motif act in one pathway, and UNC-34 and the UNC-40 P1 motif act in the other. Thus, UNC-40 might act as a scaffold to deliver several independent signals to the actin cytoskeleton.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin Cytoskeleton / genetics
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Actin Cytoskeleton / metabolism
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Animals
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Caenorhabditis elegans
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism*
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Cell Communication / physiology*
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Cell Differentiation / physiology*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Genes, Suppressor / physiology
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Growth Cones / metabolism*
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Growth Cones / ultrastructure
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism
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Mutation / genetics
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Nervous System / cytology
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Nervous System / embryology*
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Nervous System / metabolism
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Nervous System Malformations / genetics
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Nervous System Malformations / pathology
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Netrin Receptors
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Phenotype
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Promoter Regions, Genetic / genetics
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Protein Structure, Tertiary / genetics
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism*
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Recombinant Fusion Proteins
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Signal Transduction / genetics*
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rac GTP-Binding Proteins / genetics
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rac GTP-Binding Proteins / metabolism
Substances
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CED-10 protein, C elegans
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Caenorhabditis elegans Proteins
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Cell Adhesion Molecules
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DNA-Binding Proteins
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ENA-VASP proteins
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Microfilament Proteins
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Netrin Receptors
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Receptors, Cell Surface
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Recombinant Fusion Proteins
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UNC-115 protein, C elegans
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UNC-40 protein, C elegans
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rac GTP-Binding Proteins