Common and Distinctive Functions of the Hippo Effectors Taz and Yap in Skeletal Muscle Stem Cell Function
| Autor: | Sun, Congshan, De Mello, Vanessa, Mohamed, Abdalla, Ortuste Quiroga, Huascar P., Garcia‐Munoz, Amaya, Al Bloshi, Abdullah, Tremblay, Annie M., von Kriegsheim, Alexander, Collie‐Duguid, Elaina, Vargesson, Neil, Matallanas, David, Wackerhage, Henning, Zammit, Peter S. |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Taz
Satellite Cells Skeletal Muscle Tead Muscle Fibers Skeletal Muscle Stem Cells / Satellite Cells Cell Cycle Proteins Protein Serine-Threonine Kinases Muscle Development Tissue‐Specific Stem Cells Cell Fusion Myoblasts Cell Signaling Satellite cells Muscle stem cells Journal Article Animals Regeneration Hippo Signaling Pathway Muscle Skeletal Wnt Signaling Pathway Adaptor Proteins Signal Transducing Cell Proliferation Feedback Physiological Mice Knockout Stem Cells Cell Differentiation YAP-Signaling Proteins Phosphoproteins Adult Stem Cells Gene Expression Regulation Trans-Activators Yap Muscle Regeneration |
| Zdroj: | Stem Cells (Dayton, Ohio) Sun, C, De Mello, V, Mohamed, A, Ortuste Quiroga, H P, Garcia-Munoz, A, Al Bloshi, A, Tremblay, A M, von Kriegsheim, A, Collie-Duguid, E, Vargesson, N, Matallanas, D, Wackerhage, H & Zammit, P S 2017, ' Common and Distinctive Functions of the Hippo Effectors Taz and Yap in Skeletal Muscle Stem Cell Function ', Stem cells (Dayton, Ohio) . https://doi.org/10.1002/stem.2652 Sun, C, De Mello, V, Mohamed, A, Ortuste Quiroga, H P, Garcia-Munoz, A, Al Bloshi, A, Tremblay, A M, Von Kriegsheim, A, Collie-Duguid, E, Vargesson, N, Matallanas, D, Wackerhage, H & Zammit, P S 2017, ' Common and Distinctive Functions of the Hippo Effectors Taz and Yap in Skeletal Muscle Stem Cell Function ', STEM CELLS . https://doi.org/10.1002/stem.2652 |
| ISSN: | 1549-4918 1066-5099 |
| Popis: | Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analyzed Taz in vivo and ex vivo in comparison with Yap. Small interfering RNA knockdown or retroviral-mediated expression of wild-type human or constitutively active TAZ mutants in satellite cells showed that TAZ promoted proliferation, a function shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation. Functionally, while muscle growth was mildly affected in Taz (gene Wwtr1-/-) knockout (KO) mice, there were no overt effects on regeneration. Conversely, conditional KO of Yap in satellite cells of Pax7Cre-ERT2/+: Yapfl°x/fl°x: Rosa26Lacz mice produced a marked regeneration deficit. To identify potential mechanisms, microarray analysis showed many common TAZ/YAP target genes, but TAZ also regulates some genes independently of YAP, including myogenic genes such as Pax7, Myf5, and Myod1 (ArrayExpress-E-MTAB-5395). Proteomic analysis revealed many novel binding partners of TAZ/YAP in myogenic cells, but TAZ also interacts with proteins distinct from YAP that are often involved in myogenesis and aspects of cytoskeleton organization (ProteomeXchange-PXD005751). Neither TAZ nor YAP bind members of the Wnt destruction complex but both regulated expression of Wnt and Wnt-cross talking genes with known roles in myogenesis. Finally, TAZ operates through Tead4 to enhance myogenic differentiation. In summary, Taz and Yap have overlapping functions in promoting myoblast proliferation but Taz then switches to enhance myogenic differentiation. |
| Databáze: | OpenAIRE |
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