The Journal of cell biology, 2018-04, Vol.217 (4), p.1431-1451
2018
Details
- Autor(en) / Beteiligte
- Titel
- Kindlin-2 regulates mesenchymal stem cell differentiation through control of YAP1/TAZ
- Ist Teil von
- The Journal of cell biology, 2018-04, Vol.217 (4), p.1431-1451
- Ort / Verlag
- United States: Rockefeller University Press
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9525eISSN: 1540-8140DOI: 10.1083/jcb.201612177Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5881491
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing - genetics, Adaptor Proteins, Signal Transducing - metabolism, Adhesion, Adipogenesis, Animals, Biocompatibility, Biomedical materials, Cell Cycle Proteins, Cell Differentiation, Cell Lineage, Chains, Cytoskeletal Proteins - deficiency, Cytoskeletal Proteins - genetics, Cytoskeletal Proteins - metabolism, Differentiation (biology), Focal Adhesions - metabolism, HEK293 Cells, Homeodomain Proteins - genetics, Homeodomain Proteins - metabolism, Humans, Intracellular Signaling Peptides and Proteins - genetics, Intracellular Signaling Peptides and Proteins - metabolism, Intracellular signalling, Mechanotransduction, Cellular, Membrane Proteins - genetics, Membrane Proteins - metabolism, Mesenchymal Stem Cells - metabolism, Mesenchyme, Mice, Knockout, Mice, Nude, Muscle Proteins - deficiency, Muscle Proteins - genetics, Muscle Proteins - metabolism, Myosin, Myosin Light Chains - metabolism, Myosin-light-chain kinase, Myosin-Light-Chain Kinase - metabolism, Neoplasm Proteins - genetics, Neoplasm Proteins - metabolism, Osteogenesis, Phosphoproteins - genetics, Phosphoproteins - metabolism, Phosphorylation, Proteins, Regeneration, Repressor Proteins - metabolism, rhoA GTP-Binding Protein - metabolism, RhoA protein, Stem Cell Niche, Stem cells, Stress Fibers - metabolism, Tissue engineering, Trans-Activators, Transcription, Transcription Factors, Ubiquitin, Ubiquitin-protein ligase, Ubiquitin-Protein Ligases - metabolism, Yes-associated protein