COORDINATE EXPRESSION OF ALPHA-TROPOMYOSIN AND CALDESMON ISOFORMS IN ASSOCIATION WITH PHENOTYPIC MODULATION OF SMOOTH-MUSCLE CELLS

Isoform diversity of tropomyosin is generated from the limited genes b y a combination of differential transcription and alternative splicing . In the case of the alpha-tropomyosin (alpha-TM) gene, exon 2a rather than exon 2b is specifically spliced in alpha-TM-SM mRNA, which is on e of the major tropomyosin isoforms in smooth muscle cells. Here we de monstrate that expressions of cr-tropomyosin and caldesmon isoforms ar e coordinately regulated in association with phenotypic modulation of smooth muscle cells. Molecular cloning and Western and Northern blotti ngs have revealed that in addition to the downregulation of beta-TM-SM , alpha-TM-SM converted to alpha-TM-F1 and alpha-TM-F2 by a selectiona l change from exon 2a to exon 2b during dedifferentiation of smooth mu scle cells in culture. Simultaneously, a change of caldesmon isoforms from high M-r type to low M-r type was also observed by alternative se lection between exons 3b and 4 in the caldesmon gene during this proce ss. In contrast, cultured smooth muscle cells maintaining a differenti ated phenotype continued to express alpha-TM-SM, beta-TM-SM, and high M-r caldesmon. In situ hybridization revealed specific coexpression of alpha-TM-SM and high M-r caldesmon in smooth muscle in developing emb ryos. These results suggest a common splicing mechanism for phenotype- dependent expression of tropomyosin and caldesmon isoforms in both vis ceral and vascular smooth muscle cells.