Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 5745K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Miller, A. L. Articles by Koleske, A. J. Search for Related Content PubMed PubMed Citation Articles by Miller, A. L. Articles by Koleske, A. J. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Related Collections Related Article Social Bookmarking                            What's this?

The Abl-related gene (Arg) requires its F-actin–microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion

¹ Department of Molecular Biophysics and Biochemistry, Cellular, and Developmental Biology
² Department of Molecular, Cellular, and Developmental Biology
³ Department of Cell Biology, Yale University, New Haven, CT 06520
⁴ Department of Pathology, Yale University, New Haven, CT 06520
⁵ Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520

Address correspondence to Anthony J. Koleske, Department of Molecular Biophysics and Biochemistry, Yale University, SHMC-E31, 333 Cedar St., New Haven, CT 06520. Tel.: (203) 785-5624. Fax: (203) 785-7979. email: anthony.koleske{at}yale.edu

Microtubules (MTs) help establish and maintain cell polarity by promoting actin-dependent membrane protrusion at the leading edge of the cell, but the molecular mechanisms that mediate cross-talk between actin and MTs during this process are unclear. We demonstrate that the Abl-related gene (Arg) nonreceptor tyrosine kinase is required for dynamic lamellipodial protrusions after adhesion to fibronectin. arg^–/– fibroblasts exhibit reduced lamellipodial dynamics as compared with wild-type fibroblasts, and this defect can be rescued by reexpression of an Arg-yellow fluorescent protein fusion. We show that Arg can bind MTs with high affinity and cross-link filamentous actin (F-actin) bundles and MTs in vitro. MTs concentrate and insert into Arg-induced F-actin–rich cell protrusions. Arg requires both its F-actin–binding domains and its MT-binding domain to rescue the defects in lamellipodial dynamics of arg^–/– fibroblasts. These findings demonstrate that Arg can mediate physical contact between F-actin and MTs at the cell periphery and that this cross-linking activity is required for Arg to regulate lamellipodial dynamics in fibroblasts.

Key Words: cytoskeleton; actin; microtubules; protein-tyrosine kinase; Arg tyrosine kinase

The online version of this article contains supplemental material.

Abbreviations used in this paper: Arg, Abl-related gene; MT, microtubule.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

Arg links actin and microtubules

William A. Wells
J. Cell Biol. 2004 165: 294-295. [Full Text] [PDF]

This article has been cited by other articles:

• Choi, Y., Seeliger, M. A., Panjarian, S. B., Kim, H., Deng, X., Sim, T., Couch, B., Koleske, A. J., Smithgall, T. E., Gray, N. S. (2009). N-Myristoylated c-Abl Tyrosine Kinase Localizes to the Endoplasmic Reticulum upon Binding to an Allosteric Inhibitor. J. Biol. Chem. 284: 29005-29014 [Abstract] [Full Text]  
• Bradley, W. D., Koleske, A. J. (2009). Regulation of cell migration and morphogenesis by Abl-family kinases: emerging mechanisms and physiological contexts. J. Cell Sci. 122: 3441-3454 [Abstract] [Full Text]  
• Lapetina, S., Mader, C. C., Machida, K., Mayer, B. J., Koleske, A. J. (2009). Arg interacts with cortactin to promote adhesion-dependent cell edge protrusion. JCB 185: 503-519 [Abstract] [Full Text]  
• Yogalingam, G., Pendergast, A. M. (2008). Abl Kinases Regulate Autophagy by Promoting the Trafficking and Function of Lysosomal Components. J. Biol. Chem. 283: 35941-35953 [Abstract] [Full Text]  
• Cao, X., Tanis, K. Q., Koleske, A. J., Colicelli, J. (2008). Enhancement of ABL Kinase Catalytic Efficiency by a Direct Binding Regulator Is Independent of Other Regulatory Mechanisms. J. Biol. Chem. 283: 31401-31407 [Abstract] [Full Text]  
• Huang, Y., Comiskey, E. O., Dupree, R. S., Li, S., Koleske, A. J., Burkhardt, J. K. (2008). The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse. Blood 112: 111-119 [Abstract] [Full Text]  
• Stevens, T. L., Rogers, E. M., Koontz, L. M., Fox, D. T., Homem, C. C.F., Nowotarski, S. H., Artabazon, N. B., Peifer, M. (2008). Using Bcr-Abl to Examine Mechanisms by Which Abl Kinase Regulates Morphogenesis in Drosophila. Mol. Biol. Cell 19: 378-393 [Abstract] [Full Text]  
• Peacock, J. G., Miller, A. L., Bradley, W. D., Rodriguez, O. C., Webb, D. J., Koleske, A. J. (2007). The Abl-related Gene Tyrosine Kinase Acts through p190RhoGAP to Inhibit Actomyosin Contractility and Regulate Focal Adhesion Dynamics upon Adhesion to Fibronectin. Mol. Biol. Cell 18: 3860-3872 [Abstract] [Full Text]  
• Ren, N., Charlton, J., Adler, P. N. (2007). The flare Gene, Which Encodes the AIP1 Protein of Drosophila, Functions to Regulate F-Actin Disassembly in Pupal Epidermal Cells. Genetics 176: 2223-2234 [Abstract] [Full Text]  
• Bradley, W. D., Hernandez, S. E., Settleman, J., Koleske, A. J. (2006). Integrin Signaling through Arg Activates p190RhoGAP by Promoting Its Binding to p120RasGAP and Recruitment to the Membrane. Mol. Biol. Cell 17: 4827-4836 [Abstract] [Full Text]  
• Martin, M., Ahern-Djamali, S. M., Hoffmann, F. M., Saxton, W. M. (2005). Abl Tyrosine Kinase and Its Substrate Ena/VASP Have Functional Interactions with Kinesin-1. Mol. Biol. Cell 16: 4225-4230 [Abstract] [Full Text]  
• Moresco, E. M. Y., Donaldson, S., Williamson, A., Koleske, A. J. (2005). Integrin-Mediated Dendrite Branch Maintenance Requires Abelson (Abl) Family Kinases. J. Neurosci. 25: 6105-6118 [Abstract] [Full Text]  
• Woodring, P. J., Hunter, T., Wang, J. Y. J. (2005). Mitotic Phosphorylation Rescues Abl from F-actin-mediated Inhibition. J. Biol. Chem. 280: 10318-10325 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents