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J. Biol. Chem., Vol. 282, Issue 10, 7512-7521, March 9, 2007

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The Coxsackie and Adenovirus Receptor Binds Microtubules and Plays a Role in Cell Migration^*

Patrick T. Fok¹², Kuo-Cheng Huang^¶13, Paul C. Holland^¶, and Josephine Nalbantoglu^¶4

From the Montreal Neurological Institute and Departments of ^¶Neurology & Neurosurgery and Experimental Medicine, McGill University, Montreal, Quebec H3A 2B4, Canada

The Coxsackie and adenovirus receptor (CAR), a cell adhesion molecule of the immunoglobulin superfamily, inhibits cell growth of a variety of tumors. The cytoplasmic domain of CAR has been implicated in decreased invasion and intracerebral growth of human U87 glioma cells. Using affinity binding, we identified tubulin as an interaction partner for the cytoplasmic domain of CAR. The interaction was specific; CAR and tubulin co-immunoprecipitated in cells expressing endogenous CAR and partially co-localized in situ. The binding of CAR to tubulin heterodimers and to microtubules was direct, with dissociation constants of 1 µM for tubulin and 32 nM for in vitro assembled microtubules. Whereas CAR-expressing U87 glioma cells had decreased migration in a chemotactic assay in Boyden chambers as compared with control cells, an effect that depended on the presence of the cytoplasmic domain of CAR, the difference was abrogated at low, non-cytotoxic doses of the taxane paclitaxel, a microtubule-stabilizing agent. These results indicate that CAR may affect cell migration through its interaction with microtubules.

Received for publication, July 31, 2006 , and in revised form, November 29, 2006.

^* This work was supported in part by Canadian Institutes of Health Research Grants MOP 53071 and MOP-74565. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Both authors contributed equally to the results of this work.

² Supported by a Canadian Institutes of Health Research MD/PhD studentship.

³ Received a studentship from Fonds de la recherche en santé du Québec.

⁴ Research Scholar of the Fonds de la recherche en santé du Québec and a Killam Scholar. To whom correspondence should be addressed: 3801 University St., Montreal, QC H3A 2B4, Canada. Tel.: 514-398-5920; E-mail: Josephine.nalbantoglu{at}mcgill.ca.

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