Mechanoregulation of SM22α/Transgelin

SM22 alpha, also named transgelin, is an actin filament associated protein in smooth muscle and fibroblasts. Three decades after its discovery, the biological function of SM22 alpha remains under investigation. Here we report a novel finding that the expression and degradation of SM22 alpha/transgelin are regulated by mechanical tension. Following a mass spectrometry identification of SM22 alpha degradation in isolated and tension-unloaded mouse aorta, we developed specific monoclonal antibodies to study the regulation of SM22 alpha in human fetal lung myofibroblast line MRC-5 and primary cultures of neonatal mouse skin fibroblasts. The level of SM22 alpha is positively related to the mechanical tension in the cytoskeleton produced by the myosin II motor in response to the stiffness of the culture matrix. Quantitative reverse transcription polymerase chain reaction demonstrated that the expression of SM22 alpha is regulated at the transcriptional level. This mechanical regulation resembles that of calponin 2, another actin filament-associated protein. Immunofluorescent staining co-localized SM22 alpha with F-actin, myosin, and calponin 2 in mouse skin fibroblasts. The close phylogenetic relationship between SM22 alpha and the calponin family supports that SM22 alpha is a calponin-like regulatory protein. The level of SM22 alpha is decreased in skin fibroblasts isolated from calponin 2 knockout mice, suggesting interrelated regulation and function of the two proteins. On the other hand, SM22 alpha expression was maximized at a matrix stiffness higher than that for calponin 2 in the same cell type, indicating differentiated regulation and tension responsiveness. The novel mechanoregulation of SM22 alpha/transgelin lays the groundwork for understanding its cellular functions.