CD98-mediated links between amino acid transport and beta(1) integrin distribution in polarized columnar epithelia

In non-polarized cells, CD98 has been shown to both influence beta (1) inte grins and heterodimerize with LAT-2, which confers amino acid transport cap ability on the LAT-2/CD98 heterodimer. Since LAT-2 is most heavily expresse d in intestine and CD98 associates with the beta (1) integrin splice form s electively found in such epithelia, we investigated the relationship and po larity of these proteins using the intestinal epithelial model Caco2-BBE. C D98 was found to selectively coimmunoprecipitate with both LAT-2 and beta ( 1) integrin, and, logically, all three proteins were polarized to the same (basolateral) domain. Furthermore, expression of CD98 in polarized epitheli a lacking human CD98 (MDCK cells) disrupted beta (1) integrin surface distr ibution and cytoskeletal architecture, suggesting that CD98 can influence i ntegrin function. Expression of a CD98 mutant lacking the specific residues conferring LAT-2 binding similarly affected cells, confirming that the lat ter effect was not due to LAT-2 sequestration. Use of CD98 truncation mutan ts suggest that a 10-amino acid domain located at the putative cytoplasmic tail/transmembrane domain interface was necessary and sufficient to induce the phenotype change. We conclude that the CD98/LAT-2 amino acid transporte r is polarized to the same domain on which beta (1) integrin resides. CD98 appears to associate with beta (1) integrin and, in doing so, may influence its function as revealed by disruption of the outside-in signaling that co nfers cytoskeletal organization. Furthermore, such findings suggest a link between classic transport events and a critical element of barrier function : integrin-mediated influences on cytoskeletal organization.