Son of sevenless directly links the Robo receptor to rac activation to control axon repulsion at the midline.
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.
Yang
Long
L
Department of Neuroscience, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.
Bashaw
Greg J
GJ
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003463:Cues; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020839:Son of Sevenless Protein, Drosophila / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000097905:Roundabout Proteins
D048868:Adaptor Proteins, Signal Transducing; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D020839:Son of Sevenless Protein, Drosophila; D020744:rac GTP-Binding Proteins; D000097905:Roundabout Proteins; C099753:dock protein, Drosophila