Pak functions downstream of Dock to regulate photoreceptor axon guidance in Drosophila

Cell. 1999 Jun 25;97(7):853-63. doi: 10.1016/s0092-8674(00)80798-9.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • Adaptor Proteins, Signal Transducing
  • Cdc42 protein, Drosophila
  • Drosophila Proteins
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins
  • dock protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • p21-Activated Kinases
  • GTP-Binding Proteins
  • rac GTP-Binding Proteins