Trio combines with dock to regulate Pak activity during photoreceptor axon pathfinding in Drosophila.
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.
Newsome
T P
TP
Research Institute of Molecular Pathology, Vienna, Austria.
Schmidt
S
S
Dietzl
G
G
Keleman
K
K
Asling
B
B
Debant
A
A
Dickson
B J
BJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D018076:DNA, Complementary; D004330:Drosophila / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins
D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; D029721:Drosophila Proteins; D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C099753:dock protein, Drosophila; D017346:Protein Serine-Threonine Kinases; C099628:TRIO protein, human; D054462:p21-Activated Kinases; C490974:trio protein, Drosophila; D020744:rac GTP-Binding Proteins