Cell type-specific occurrence of caveolin-1α and -1β in the lung caused by expression of distinct mRNAs

Two isoforms of caveolin-1, alpha and beta, had been thought to be generated by alternative translation initiation of an mRNA (FL mRNA), but we showed previously that a variant mRNA (5'V mRNA) encodes the beta isoform specifically (Kogo, H., and Fujimoto, T. (2000) FEBS Lett. 465, 119-123). In the present study, we demonstrated strong correlation between the expression of the caveolin-1 protein isoforms and mRNA variants in culture cells and the developing mouse lung. The alpha isoform protein and FL mRNA were expressed constantly during the lung development, whereas expression of the alpha isoform protein and 5'V mRNA was negligible in the fetal lung before 17.5 days post-coitum, and markedly increased simultaneously at 18.5 days post coitum, when the alveolar type I cells started to differentiate. Immunohistochemical analysis revealed the cell type-specific expression of the two isoforms; the alveolar type I cell expresses the beta isoform predominantly, while the endothelium harbors the alpha isoform chiefly. The mutually exclusive expression of caveolin-1 isoforms was verified by Western blotting of the selective plasma membrane preparation obtained from the endothelial and alveolar epithelial cells. The present result indicates that the two caveolin-1 isoforms are generated from distinct mRNAs in vivo and that their production is regulated independently at the transcriptional level. The result also suggests that the alpha and beta isoforms of caveolin-1 may have unique physiological functions.