title: Coordination of satellite cell activation and self-renewal by Par-complex-dependent asymmetric activation of p38α/β MAPK.
abstract: In response to muscle injury, satellite cells activate the p38α/β MAPK pathway to exit quiescence, then proliferate, repair skeletal muscle, and self-renew, replenishing the quiescent satellite cell pool. Although satellite cells are capable of asymmetric division, the mechanisms regulating satellite cell self-renewal are not understood. We found that satellite cells, once activated, enter the cell cycle and a subset undergoes asymmetric division, renewing the satellite cell pool. Asymmetric localization of the Par complex activates p38α/β MAPK in only one daughter cell, inducing MyoD, which permits cell cycle entry and generates a proliferating myoblast. The absence of p38α/β MAPK signaling in the other daughter cell prevents MyoD induction, renewing the quiescent satellite cell. Thus, satellite cells employ a mechanism to generate distinct daughter cells, coupling the Par complex and p38α/β MAPK signaling to link the response to muscle injury with satellite cell self-renewal.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Troy
authors.forename: Adam B
authors.initials: AB
authors.lastname: Cadwallader
authors.forename: Yuri
authors.initials: Y
authors.lastname: Fedorov
authors.forename: Kristina
authors.initials: K
authors.lastname: Tyner
authors.forename: Kathleen Kelly
authors.initials: KK
authors.lastname: Tanaka
authors.forename: Bradley B
authors.initials: BB
authors.lastname: Olwin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D060049:Asymmetric Cell Division; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D004789:Enzyme Activation / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D024510:Muscle Development; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D018008:Myogenin / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000099293:Protein Kinase C-lambda
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D007527:Isoenzymes; D046912:Multiprotein Complexes; D017570:MyoD Protein; D018008:Myogenin; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D000099293:Protein Kinase C-lambda; C115084:Pard3 protein, mouse