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Published 10 May 2004. doi:10.1083/jcb.200308055
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 165, Number 3, 407-419
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Article

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

Ann L. Miller1, Yinxiang Wang1, Mark S. Mooseker2,3,4, and Anthony J. Koleske1,5

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

Y. Wang made significant contributions to this paper.

The online version of this article contains supplemental material.

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


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