Pak functions downstream of Dock to regulate photoreceptor axon guidance in Drosophila.
The SH2/SH3 adaptor protein Dock has been proposed to transduce signals from guidance receptors to the actin cytoskeleton in Drosophila photoreceptor (R cell) growth cones. Here, we demonstrate that Drosophila p21-activated kinase (Pak) is required in a Dock pathway regulating R cell axon guidance and targeting. Dock and Pak colocalize to R cell axons and growth cones, physically interact, and their loss-of-function phenotypes are indistinguishable. Normal patterns of R cell connectivity require Pak's kinase activity and binding sites for both Dock and Cdc42/Rac. A membrane-tethered form of Pak (Pak(myr) acts as a dominant gain-of-function protein. Retinal expression of Pak(myr) rescues the R cell connectivity phenotype in dock mutants. These data establish Pak as a critical regulator of axon guidance and a downstream effector of Dock in vivo.
Howard Hughes Medical Institute, Department of Biological Chemistry, School of Medicine, University of California, Los Angeles 90095, USA.
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Zipursky
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites; D002462:Cell Membrane; D004330:Drosophila / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins; D019204:GTP-Binding Proteins / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins
D048868:Adaptor Proteins, Signal Transducing; C090145:Cdc42 protein, Drosophila; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C099753:dock protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins