Trio combines with dock to regulate Pak activity during photoreceptor axon pathfinding in Drosophila

T P Newsome; S Schmidt; G Dietzl; K Keleman; B Asling; A Debant; B J Dickson

doi:10.1016/s0092-8674(00)80838-7

Trio combines with dock to regulate Pak activity during photoreceptor axon pathfinding in Drosophila

Cell. 2000 Apr 28;101(3):283-94. doi: 10.1016/s0092-8674(00)80838-7.

Authors

T P Newsome¹, S Schmidt, G Dietzl, K Keleman, B Asling, A Debant, B J Dickson

Affiliation

¹ Research Institute of Molecular Pathology, Vienna, Austria.

PMID: 10847683
DOI: 10.1016/s0092-8674(00)80838-7

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

Adaptor Proteins, Signal Transducing
DNA, Complementary
Drosophila Proteins
Guanine Nucleotide Exchange Factors
Nerve Tissue Proteins
Phosphoproteins
dock protein, Drosophila
Protein Serine-Threonine Kinases
TRIO protein, human
p21-Activated Kinases
trio protein, Drosophila
rac GTP-Binding Proteins

Associated data

GENBANK/AF215635
GENBANK/AF238044