Rapid microtubule-dependent induction of neurite-like extensions in NIH 3T3 fibroblasts by inhibition of ROCK and Cbl.
A number of key cellular functions, such as morphological differentiation and cell motility, are closely associated with changes in cytoskeletal dynamics. Many of the principal signaling components involved in actin cytoskeletal dynamics have been identified, and these have been shown to be critically involved in cell motility. In contrast, signaling to microtubules remains relatively uncharacterized, and the importance of signaling pathways in modulation of microtubule dynamics has so far not been established clearly. We report here that the Rho-effector ROCK and the multiadaptor proto-oncoprotein Cbl can profoundly affect the microtubule cytoskeleton. Simultaneous inhibition of these two signaling molecules induces a dramatic rearrangement of the microtubule cytoskeleton into microtubule bundles. The formation of these microtubule bundles, which does not involve signaling by Rac, Cdc42, Crk, phosphatidylinositol 3-kinase, and Abl, is sufficient to induce distinct neurite-like extensions in NIH 3T3 fibroblasts, even in the absence of microfilaments. This novel microtubule-dependent function that promotes neurite-like extensions is not dependent on net changes in microtubule polymerization or stabilization, but rather involves selective elongation and reorganization of microtubules into long bundles.
Scaife
Robin M
RM
Department of Pathology, University of Western Australia, Crawley, WA 6009, Australia. rscaife@cyllene.uwa.edu.au
Job
Didier
D
Langdon
Wallace Y
WY
D008841:Actin Cytoskeleton / Q000378:metabolism / Q000502:physiology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D022081:Cell Surface Extensions / Q000378:metabolism* / Q000502:physiology; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000378:metabolism* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D016313:Genes, abl / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008870:Microtubules / Q000378:metabolism* / Q000502:physiology; D041681:NIH 3T3 Cells; D050722:Oncogene Protein v-cbl; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D011725:Pyridines / Q000494:pharmacology; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism* / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D050722:Oncogene Protein v-cbl; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011725:Pyridines; D015682:Retroviridae Proteins, Oncogenic; D020764:cdc42 GTP-Binding Protein; D054460:rho-Associated Kinases; C108830:Y 27632