Abstract
Crossing the midline produces changes in axons such that they are no longer attracted to the midline. In Drosophila, Roundabout reaches high levels on axons once they have crossed the midline, and this prohibits recrossing. Roundabout protein levels are regulated by Commissureless. We show that Commissureless binds to and is regulated by the ubiquitin ligase DNedd4. We further show that the ability of Commissureless to regulate Roundabout protein levels requires an intact DNedd4 binding site and ubiquitin acceptor sites within the Commissureless protein. The ability of Commissureless to regulate Robo in the embryo also requires a Commissureless/DNedd4 interaction. Our results show that changes in axonal sensitivity to external cues during pathfinding across the midline makes use of ubiquitin-dependent mechanisms to regulate transmembrane protein levels.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Axons / enzymology*
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Axons / ultrastructure
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / isolation & purification*
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Cell Communication / physiology*
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Cell Differentiation / physiology*
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Cell Membrane / metabolism
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Drosophila Proteins*
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Drosophila melanogaster / cytology
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Drosophila melanogaster / embryology
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Drosophila melanogaster / enzymology*
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Endosomal Sorting Complexes Required for Transport
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Functional Laterality / genetics
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Gene Expression Regulation, Developmental / physiology
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Gene Expression Regulation, Enzymologic / physiology
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Growth Cones / metabolism
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Growth Cones / ultrastructure
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Intracellular Fluid / metabolism
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Ligases / genetics
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Ligases / isolation & purification*
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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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Nedd4 Ubiquitin Protein Ligases
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Nerve Tissue Proteins
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Nervous System / cytology
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Nervous System / embryology
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Nervous System / enzymology*
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Protein Binding / physiology
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Protein Structure, Tertiary / physiology
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Protein Transport / physiology
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Receptors, Cell Surface / metabolism
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Receptors, Immunologic / metabolism*
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Roundabout Proteins
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Sequence Homology, Amino Acid
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Sequence Homology, Nucleic Acid
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Transport Vesicles / metabolism
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Ubiquitin / metabolism
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Ubiquitin-Protein Ligases*
Substances
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Calcium-Binding Proteins
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DNA, Complementary
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Drosophila Proteins
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Endosomal Sorting Complexes Required for Transport
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Membrane Proteins
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Nerve Tissue Proteins
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Receptors, Cell Surface
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Receptors, Immunologic
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Ubiquitin
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comm protein, Drosophila
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Nedd4 Ubiquitin Protein Ligases
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Ubiquitin-Protein Ligases
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Ligases