Dosage-sensitive, reciprocal genetic interactions between the Abl tyrosine kinase and the putative GEF trio reveal trio's role in axon pathfinding

Neuron. 2000 Apr;26(1):107-18. doi: 10.1016/s0896-6273(00)81142-3.

Abstract

The Abelson tyrosine kinase (Abl) is integrated into signal transduction networks regulating axon outgrowth. We have identified the Drosophila trio gene through a mutation that exacerbates the Abl mutant phenotype. Drosophila Trio is an ortholog of mammalian Trio, a protein that contains multiple spectrin-like repeats and two Dbl homology (DH) domains that affect actin cytoskeletal dynamics via the small GTPases Rho and Rac. Phenotypic analysis demonstrates that trio and Abl cooperate in regulating axon outgrowth in the embryonic central nervous system (CNS). Dosage-sensitive interactions between trio and Abl, failed axon connections (fax), and enabled (ena) indicate that Trio is integrated into common signaling networks with these gene products. These observations suggest a mechanism by which Abl-mediated signaling networks influence the actin cytoskeleton in neuronal growth cones.

Publication types

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

MeSH terms

  • Animals
  • Axons / metabolism
  • Central Nervous System / embryology
  • Central Nervous System / metabolism
  • Drosophila
  • Drosophila Proteins*
  • Gene Dosage*
  • Genes, abl / genetics*
  • Genotype
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / physiology
  • Molecular Sequence Data
  • Mutation, Missense / genetics
  • Mutation, Missense / physiology*
  • Phenotype
  • Phosphoproteins / genetics*
  • Phosphoproteins / physiology
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / physiology
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / physiology
  • Retina / embryology*
  • Retina / metabolism

Substances

  • Drosophila Proteins
  • Guanine Nucleotide Exchange Factors
  • Phosphoproteins
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • trio protein, Drosophila

Associated data

  • GENBANK/AF216663