| First Author | Guo L | Year | 2018 |
| Journal | J Cell Biol | Volume | 217 |
| Issue | 4 | Pages | 1431-1451 |
| PubMed ID | 29496737 | Mgi Jnum | J:260481 |
| Mgi Id | MGI:6149626 | Doi | 10.1083/jcb.201612177 |
| Citation | Guo L, et al. (2018) Kindlin-2 regulates mesenchymal stem cell differentiation through control of YAP1/TAZ. J Cell Biol 217(4):1431-1451 |
| abstractText | Precise control of mesenchymal stem cell (MSC) differentiation is critical for tissue development and regeneration. We show here that kindlin-2 is a key determinant of MSC fate decision. Depletion of kindlin-2 in MSCs is sufficient to induce adipogenesis and inhibit osteogenesis in vitro and in vivo. Mechanistically, kindlin-2 regulates MSC differentiation through controlling YAP1/TAZ at both the transcript and protein levels. Kindlin-2 physically associates with myosin light-chain kinase in response to mechanical cues of cell microenvironment and intracellular signaling events and promotes myosin light-chain phosphorylation. Loss of kindlin-2 inhibits RhoA activation and reduces myosin light-chain phosphorylation, stress fiber formation, and focal adhesion assembly, resulting in increased Ser127 phosphorylation, nuclear exclusion, and ubiquitin ligase atrophin-1 interacting protein 4-mediated degradation of YAP1/TAZ. Our findings reveal a novel kindlin-2 signaling axis that senses the mechanical cues of cell microenvironment and controls MSC fate decision, and they suggest a new strategy to regulate MSC differentiation, tissue repair, and regeneration. |
