The novel {alpha}4B murine {alpha}4 integrin splicing variant inhibits {alpha}4-dependent cell adhesion [Cell Biology]

April 22nd, 2014 by Kouro, H., Kon, S., Matsumoto, N., Miyashita, T., Kakuchi, A., Ashitomi, D., Saito, K., Nakatsuru, T., Togi, S., Muromoto, R., Matsuda, T.

Integrins affect the motility of multiple cell types to control cell survival, growth, or differentiation, which are mediated by cell-cell and cell-extracellular matrix interactions. We previously reported that the α9 integrin splicing variant, SFα9, promotes wild-type (WT) α9 integrin-dependent adhesion. In this study, we introduced a new murine α4 integrin splicing variant, α4B, which has a novel short cytoplasmic tail. In inflamed tissues, the expression of α4B, as well as WT α4 integrin, was up-regulated. Cells expressing α4B specifically bound to VCAM-1, but not other α4 integrin ligands such as fibronectin CS1 or osteopontin. The binding of cells expressing WT α4 integrin to α4 integrin ligands is inhibited by co-expression of α4B. Knockdown of α4B in metastatic melanoma cell lines results in a significant increase of lung metastasis. Expression levels of WT α4 integrin are unaltered by α4B; with α4B acting as a regulatory subunit for WT α4 integrin by dominant-negative effect or inhibiting α4 integrin activation.