title: Sox4-mediated caldesmon expression facilitates differentiation of skeletal myoblasts.
abstract: Caldesmon (CaD), which was originally identified as an actin-regulatory protein, is involved in the regulation of diverse actin-related signaling processes, including cell migration and proliferation, in various cells. The cellular function of CaD has been studied primarily in the smooth muscle system; nothing is known about its function in skeletal muscle differentiation. In this study, we found that the expression of CaD gradually increased as differentiation of C2C12 myoblasts progressed. Silencing of CaD inhibited cell spreading and migration, resulting in a decrease in myoblast differentiation. Promoter analysis of the caldesmon gene (Cald1) and gel mobility shift assays identified Sox4 as a major trans-acting factor for the regulation of Cald1 expression during myoblast differentiation. Silencing of Sox4 decreased not only CaD protein synthesis but also myoblast fusion in C2C12 cells and myofibril formation in mouse embryonic muscle. Overexpression of CaD in Sox4-silenced C2C12 cells rescued the differentiation process. These results clearly demonstrate that CaD, regulated by Sox4 transcriptional activity, contributes to skeletal muscle differentiation.
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 156-756, Korea.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Jang
authors.forename: Jung-Woong
authors.initials: JW
authors.lastname: Kim
authors.forename: Daehwan
authors.initials: D
authors.lastname: Kim
authors.forename: Chul-Hong
authors.initials: CH
authors.lastname: Kim
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: An
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Choi
authors.forename: Sangmyung
authors.initials: S
authors.lastname: Rhee
mesh_terms: D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D024510:Muscle Development / Q000235:genetics; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D055751:SOXC Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D002148:Calmodulin-Binding Proteins; D055751:SOXC Transcription Factors; C489990:Sox4 protein, mouse
keywords: Caldesmon; Skeletal muscle differentiation; Transcription factor Sox4