Cell Type-specific Occurrence of Caveolin-1α and -1β in the Lung Caused by Expression of Distinct mRNAs

Abstract

Two isoforms of caveolin-1, α and β, 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 β 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 α isoform protein and FL mRNA were expressed constantly during the lung development, whereas expression of the β 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 β isoform predominantly, while the endothelium harbors the α 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 α and β isoforms of caveolin-1 may have unique physiological functions. Two isoforms of caveolin-1, α and β, 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 β 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 α isoform protein and FL mRNA were expressed constantly during the lung development, whereas expression of the β 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 β isoform predominantly, while the endothelium harbors the α 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 α and β isoforms of caveolin-1 may have unique physiological functions.