RRC ID 30436
Author Newsome TP, Schmidt S, Dietzl G, Keleman K, Asling B, Debant A, Dickson BJ.
Title Trio combines with dock to regulate Pak activity during photoreceptor axon pathfinding in Drosophila.
Journal Cell
Abstract Correct pathfinding by Drosophila photoreceptor axons requires recruitment of p21-activated kinase (Pak) to the membrane by the SH2-SH3 adaptor Dock. Here, we identify the guanine nucleotide exchange factor (GEF) Trio as another essential component in photoreceptor axon guidance. Regulated exchange activity of one of the two Trio GEF domains is critical for accurate pathfinding. This GEF domain activates Rac, which in turn activates Pak. Mutations in trio result in projection defects similar to those observed in both Pak and dock mutants, and trio interacts genetically with Rac, Pak, and dock. These data define a signaling pathway from Trio to Rac to Pak that links guidance receptors to the growth cone cytoskeleton. We propose that distinct signals transduced via Trio and Dock act combinatorially to activate Pak in spatially restricted domains within the growth cone, thereby controlling the direction of axon extension.
Volume 101(3)
Pages 283-94
Published 2000-4-28
DOI 10.1016/s0092-8674(00)80838-7
PII S0092-8674(00)80838-7
PMID 10847683
MeSH Adaptor Proteins, Signal Transducing Animals Animals, Genetically Modified Axons / physiology* Base Sequence Cell Membrane / metabolism DNA, Complementary Drosophila / genetics Drosophila / metabolism Drosophila / physiology Drosophila Proteins* Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism* Humans Molecular Sequence Data Mutagenesis Nerve Tissue Proteins / metabolism* Phosphoproteins / genetics Phosphoproteins / metabolism* Photoreceptor Cells, Invertebrate / cytology* Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* p21-Activated Kinases rac GTP-Binding Proteins
IF 38.637
Times Cited 242
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
Drosophila DGRC#109893 DGRC#109899 DGRC#109910 DGRC#109912 DGRC#109917