Abstract
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.
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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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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Axons / metabolism
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Axons / physiology*
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Binding Sites
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Cell Membrane
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Drosophila / metabolism
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Drosophila / physiology
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Drosophila Proteins*
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GTP-Binding Proteins / metabolism
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Growth Cones / metabolism
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Molecular Sequence Data
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Mutagenesis
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Photoreceptor Cells, Invertebrate / metabolism*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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p21-Activated Kinases
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rac GTP-Binding Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Cdc42 protein, Drosophila
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Drosophila Proteins
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Nerve Tissue Proteins
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Recombinant Fusion Proteins
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dock protein, Drosophila
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Protein Serine-Threonine Kinases
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p21-Activated Kinases
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GTP-Binding Proteins
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rac GTP-Binding Proteins