The microtubule plus end tracking protein Orbit/MAST/CLASP acts downstream of the tyrosine kinase Abl in mediating axon guidance

Neuron. 2004 Jun 24;42(6):913-26. doi: 10.1016/j.neuron.2004.05.020.

Abstract

Axon guidance requires coordinated remodeling of actin and microtubule polymers. Using a genetic screen, we identified the microtubule-associated protein Orbit/MAST as a partner of the Abelson (Abl) tyrosine kinase. We find identical axon guidance phenotypes in orbit/MAST and Abl mutants at the midline, where the repellent Slit restricts axon crossing. Genetic interaction and epistasis assays indicate that Orbit/MAST mediates the action of Slit and its receptors, acting downstream of Abl. We find that Orbit/MAST protein localizes to Drosophila growth cones. Higher-resolution imaging of the Orbit/MAST ortholog CLASP in Xenopus growth cones suggests that this family of microtubule plus end tracking proteins identifies a subset of microtubules that probe the actin-rich peripheral growth cone domain, where guidance signals exert their initial influence on cytoskeletal organization. These and other data suggest a model where Abl acts as a central signaling node to coordinate actin and microtubule dynamics downstream of guidance receptors.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • Animals, Genetically Modified
  • Axons / physiology*
  • Cells, Cultured
  • Central Nervous System / cytology
  • Central Nervous System / embryology
  • Central Nervous System / metabolism
  • Drosophila
  • Drosophila Proteins / physiology*
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Gene Expression Regulation
  • Genetic Testing / methods
  • Green Fluorescent Proteins
  • Growth Cones / physiology*
  • Humans
  • Immunohistochemistry / methods
  • In Situ Hybridization
  • Luminescent Proteins / metabolism
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / physiology*
  • Microtubules / metabolism
  • Models, Biological
  • Mutation
  • Neoplasm Proteins
  • Nuclear Proteins / metabolism
  • Oncogene Proteins v-abl / metabolism
  • Oncogene Proteins v-abl / physiology*
  • Phenotype
  • Time Factors
  • Xenopus

Substances

  • Actins
  • Clasp protein, mouse
  • Drosophila Proteins
  • Luminescent Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Oncogene Proteins v-abl
  • chb protein, Drosophila
  • Green Fluorescent Proteins
  • cytoplasmic linker protein 170