CELL TYPE-SPECIFIC INTEGRIN VARIANTS WITH ALTERNATIVE ALPHA-CHAIN CYTOPLASMIC DOMAINS

The integrin heterodimers composed of the alpha-6 subunit with the beta-1 or beta-4 subunit (alpha-6-beta-4 and alpha-6-beta-4) are receptors for laminin and basement membrane components, respectively. The alpha-3-beta-1 integrin recognizes laminin, collagen, fibronectin, or epiligrin. We report the identification of structural variants (A and B) of the alpha-6 and alpha-3 subunits, containing distinct cytoplasmic domains. The expression of one cytoplasmic domain or the other, based probably on alternative exon usage, is cell-type dependent. Most transformed cell lines express both alpha-6A and alpha-6B isoforms, as determined by mRNA amplification or antibody immunoprecipitation. In contrast, embryonic fibroblasts express exclusively alpha-6A, and embryonic stem cells express exclusively alpha-6B. In most normal tissues, both alpha-6 isoforms are detectable, but several tissues express either alpha-6A or alpha-6B. The alpha-3B mRNA was amplified from heart and brain, while all other tissues and cell lines tested contained only alpha-3A mRNA. Alternative cytoplasmic domains may provide a means for varying the cellular responses to the ligands of alpha-6 and alpha-3 integrins according to the cell type.