Abstract
The netrin UNC-6 repels motor axons by activating the UNC-5 receptor alone or in combination with the UNC-40/DCC receptor. In a genetic screen for C. elegans mutants exhibiting partial defects in motor axon projections, we isolated the max-1 gene (required for motor neuron axon guidance). max-1 loss-of-function mutations cause fully penetrant but variable axon guidance defects. Mutations in unc-5 and unc-6, but not in unc-40, dominantly enhance the mutant phenotypes of max-1, whereas overexpression of unc-5 or unc-6, but not of unc-40, bypasses the requirement for max-1. MAX-1 proteins contain PH, MyTH4, and FERM domains and appear to be localized to neuronal processes. Human MAX-1 and UNC5H2 colocalize in discrete subcellular regions of transfected cells. Our results suggest a possible role for MAX-1 in netrin-induced axon repulsion by modulating the UNC-5 receptor signaling pathway.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Caenorhabditis elegans / cytology
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Caenorhabditis elegans / embryology*
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / isolation & purification*
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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 / genetics*
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Cell Differentiation / genetics*
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Chromosome Mapping
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Cytoplasm / metabolism
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Gene Expression Regulation, Developmental / genetics
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Growth Cones / metabolism*
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Growth Cones / ultrastructure
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Helminth Proteins / genetics
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Helminth Proteins / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Molecular Sequence Data
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Motor Neurons / cytology
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Motor Neurons / metabolism
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Nerve Growth Factors / metabolism
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / isolation & purification*
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Nerve Tissue Proteins / metabolism
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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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Netrin Receptors
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Netrin-1
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Netrins
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Neural Pathways / cytology
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Neural Pathways / embryology*
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Neural Pathways / metabolism
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Neurites / metabolism
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Neurites / ultrastructure
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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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Receptors, Growth Factor / genetics
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Receptors, Growth Factor / metabolism
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Tumor Suppressor Proteins
Substances
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Caenorhabditis elegans Proteins
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Cell Adhesion Molecules
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Helminth Proteins
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Membrane Proteins
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Nerve Growth Factors
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Nerve Tissue Proteins
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Netrin Receptors
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Netrins
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Receptors, Cell Surface
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Receptors, Growth Factor
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Tumor Suppressor Proteins
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UNC-40 protein, C elegans
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UNC-6 protein, C elegans
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max-1 protein, C elegans
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UNC-5 protein, C elegans
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Netrin-1