Abstract
Son of sevenless (Sos) is a dual specificity guanine nucleotide exchange factor (GEF) that regulates both Ras and Rho family GTPases and thus is uniquely poised to integrate signals that affect both gene expression and cytoskeletal reorganization. Here, using genetics, biochemistry, and cell biology, we demonstrate that Sos is recruited to the plasma membrane, where it forms a ternary complex with the Roundabout receptor and the SH3-SH2 adaptor protein Dreadlocks (Dock) to regulate Rac-dependent cytoskeletal rearrangement in response to the Slit ligand. Intriguingly, the Ras and Rac-GEF activities of Sos can be uncoupled during Robo-mediated axon repulsion; Sos axon guidance function depends on its Rac-GEF activity, but not its Ras-GEF activity. These results provide in vivo evidence that the Ras and RhoGEF domains of Sos are separable signaling modules and support a model in which Robo recruits Sos to the membrane via Dock to activate Rac during midline repulsion.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Cell Communication / physiology
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Cell Line, Tumor
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Cell Membrane / metabolism
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Cues
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Cytoskeleton / genetics
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Cytoskeleton / metabolism
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Drosophila / cytology
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Drosophila / embryology*
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Drosophila / metabolism*
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Drosophila Proteins
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Gene Expression Regulation, Developmental / physiology
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Growth Cones / metabolism*
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Growth Cones / ultrastructure
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Humans
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Nerve Tissue Proteins / genetics
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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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Protein Structure, Tertiary / physiology
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Protein Transport / physiology
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Roundabout Proteins
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Signal Transduction / physiology
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Son of Sevenless Protein, Drosophila / chemistry
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Son of Sevenless Protein, Drosophila / genetics
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Son of Sevenless Protein, Drosophila / metabolism*
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rac GTP-Binding Proteins / genetics
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rac GTP-Binding Proteins / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Drosophila Proteins
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Nerve Tissue Proteins
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Receptors, Immunologic
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Son of Sevenless Protein, Drosophila
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dock protein, Drosophila
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rac GTP-Binding Proteins