The microtubule plus end tracking protein Orbit/MAST/CLASP acts downstream of the tyrosine kinase Abl in mediating axon guidance.
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.
Lee
Haeryun
H
Department of Cell Biology, Program in Neuroscience, Dana Farber Cancer Institute/Harvard Cancer Center and Harvard Center of Neurodegeneration and Repair, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Engel
Ulrike
U
Rusch
Jannette
J
Scherrer
Simone
S
Sheard
Katherine
K
Van Vactor
David
D
D000199:Actins / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000502:physiology*; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005786:Gene Expression Regulation; D005820:Genetic Testing / Q000379:methods; D049452:Green Fluorescent Proteins; D020439:Growth Cones / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D016374:Oncogene Proteins v-abl / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D013997:Time Factors; D014981:Xenopus
D000199:Actins; C469747:Clasp protein, mouse; D029721:Drosophila Proteins; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016374:Oncogene Proteins v-abl; C407307:chb protein, Drosophila; D049452:Green Fluorescent Proteins; C076744:cytoplasmic linker protein 170