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PMID:15207236
| Citation |
Lee, H, Engel, U, Rusch, J, Scherrer, S, Sheard, K and Van Vactor, D (2004) The microtubule plus end tracking protein Orbit/MAST/CLASP acts downstream of the tyrosine kinase Abl in mediating axon guidance. Neuron 42:913-26 |
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| 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. |
| Links |
PubMed Online version:10.1016/j.neuron.2004.05.020 |
| Keywords |
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 |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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