Nature Cell Biology6, 820 - 830 (2004)
Published online: 15 August 2004; | doi:10.1038/ncb1160
EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration
Ying Wen1, Christina H. Eng1, 2, Jan Schmoranzer1, Noemi Cabrera-Poch1, 3, Edward J. S. Morris1, Michael Chen1, Bradley J. Wallar4, 5, Arthur S. Alberts4
& Gregg G. Gundersen1
1
Department of Anatomy & Cell Biology, Columbia University, New York, NY 10032, USA.
2
Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University, New York, NY 10032, USA.
3
Current address: Instituto de Investigaciones Biomédicas "Alberto Sols" C.S.I.C.-U.A.M. C/Arturo Duperier, 4 Madrid 28029, Spain.
4
Laboratory for Cell Structure & Signal Integration, Van Andel Institute, Grand Rapids, MI 49503, USA.
5
Current address: Grand Valley State University, Chemistry Department, 368 Padnos Hall, Allendale, MI 49401, USA.
Correspondence should be addressed to Gregg G. Gundersen ggg1@columbia.edu
Lysophosphatidic acid (LPA) stimulates Rho GTPase and its effector, the formin mDia, to capture and stabilize microtubules in fibroblasts. We investigated whether mammalian EB1 and adenomatous polyposis coli (APC) function downstream of Rho−mDia in microtubule stabilization. A carboxy-terminal APC-binding fragment of EB1 (EB1-C) functioned as a dominant-negative inhibitor of microtubule stabilization induced by LPA or active mDia. Knockdown of EB1 with small interfering RNAs also prevented microtubule stabilization. Expression of either full-length EB1 or APC, but not an APC-binding mutant of EB1, was sufficient to stabilize microtubules. Binding and localization studies showed that EB1, APC and mDia may form a complex at stable microtubule ends. Furthermore, EB1-C, but not an APC-binding mutant, inhibited fibroblast migration in an in vitro wounding assay. These results show an evolutionarily conserved pathway for microtubule capture, and suggest that mDia functions as a scaffold protein for EB1 and APC to stabilize microtubules and promote cell migration.
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