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

Abstract

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 approximately 1 mum for tubulin and approximately 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.