CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression

CD147 is a broadly expressed plasma membrane glycoprotein containing two im munoglobulin-like domains and a single charge-containing transmembrane doma in. Here we use co-immunoprecipitation and chemical cross-linking to demons trate that CD147 specifically interacts with MCT1 and MCT4, two members of the proton-linked monocarboxylate (lactate) transporter family that play a fundamental role in metabolism, but not with MCT2, Studies with a CD2-CD147 chimera implicate the transmembrane and cytoplasmic domains of CD147 in th is interaction. In heart cells, CD147 and MCT1 co-localize, concentrating a t the t-tubular and intercalated disk regions. In mammalian cell lines, exp ression is uniform but cross-linking with anti-CD147 antibodies caused MCT1 , MCT4 and CD147, but not GLUT1 or MCT2, to redistribute together into 'cap s', In MCT-transfected cells, expressed protein accumulated in a perinuclea r compartment, whereas co-transfection with CD147 enabled expression of act ive MCT1 or MCT4, but not MCT2, in the plasma membrane. We conclude that CD 147 facilitates proper expression of MCT1 and MCT4 at the cell surface, whe re they remain tightly bound to each other. This association may also be im portant in determining their activity and location.