title: Kindlin 2 regulates myogenic related factor myogenin via a canonical Wnt signaling in myogenic differentiation.
abstract: Kindlin 2, as an integrin-associated protein, is required for myocyte elongation and fusion. However, the association of Kindlin 2 with muscle differentiation-related signaling pathways is unknown. Here, we identified a mechanism that Kindlin 2 regulates myogenic regulatory factors myogenin via a canonical Wnt/β-catenin signaling. We found that knockdown of Kindlin 2 leads to the abolishment of β-catenin/TCF4-mediated transcription in C2C12 cells, followed by the impairment of myogenic differentiation. Mechanistically, nuclear translocation of both Kindlin 2 and β-catenin is induced during myogenic differentiation. In particular, Kindlin 2 forms a tripartite complex with active β-catenin and TCF4, and hence co-occupied on the promoter of myogenin to enhance its expression. Functionally, depletion of Kindlin 2 impairs myogenic differentiation via downregulation of myogenin. Taken together, our data reveal that Kindlin 2 is required for Wnt signaling-regulated myogenic differentiation, providing a mechanistic insight into the role of Kindlin-2 in muscle development.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education of China, Peking University Health Science Center, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yu
authors.forename: Lihua
authors.initials: L
authors.lastname: Qi
authors.forename: Junzhou
authors.initials: J
authors.lastname: Wu
authors.forename: Yunling
authors.initials: Y
authors.lastname: Wang
authors.forename: Weigang
authors.initials: W
authors.lastname: Fang
authors.forename: Hongquan
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018008:Myogenin / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D000073940:Transcription Factor 4; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D003598:Cytoskeletal Proteins; D009124:Muscle Proteins; D018008:Myogenin; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4; D051153:Wnt Proteins; D051176:beta Catenin; C527802:kindlin-2 protein, mouse