Interaction of monocarboxylate transporter 4 with {beta}1-integrin and its role in cell migration

Department of Anatomy, Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania Submitted 20 August 2008 ; accepted in final form 9 December 2008 Monocarboxylate transporter (MCT) 4 is a heteromeric proton-coupled lactate transporter that is noncovalently linked to the extracellular matrix metalloproteinase inducer CD147 and is typically expressed in glycolytic tissues. There is increasing evidence to suggest that ion transporters are part of macromolecular complexes involved in regulating β 1 -integrin adhesion and cell movement. In the present study we examined whether MCTs play a role in cell migration through their interaction with β 1 -integrin. Using reciprocal coimmunoprecipitation assays, we found that β 1 -integrin selectively associated with MCT4 in ARPE-19 and MDCK cells, two epithelial cell lines that express both MCT1 and MCT4. In polarized monolayers of ARPE-19 cells, MCT4 and β 1 -integrin colocalized to the basolateral membrane, while both proteins were found in the leading edge lamellapodia of migrating cells. In scratch-wound assays, MCT4 knockdown slowed migration and increased focal adhesion size. In contrast, silencing MCT1 did not alter the rate of cell migration or focal adhesion size. Taken together, our findings suggest that the specific interaction of MCT4 with β 1 -integrin may regulate cell migration through modulation of focal adhesions. MCT4; CD147 Address for reprint requests and other correspondence: N. J. Philp, Dept. of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Thomas Jefferson Univ., 1020 Locust St., Philadelphia, PA 19107 (e-mail: nancy.philp{at}jefferson.edu )