The p38alpha/beta MAPK functions as a molecular switch to activate the quiescent satellite cell.
Somatic stem cells cycle slowly or remain quiescent until required for tissue repair and maintenance. Upon muscle injury, stem cells that lie between the muscle fiber and basal lamina (satellite cells) are activated, proliferate, and eventually differentiate to repair the damaged muscle. Satellite cells in healthy muscle are quiescent, do not express MyoD family transcription factors or cell cycle regulatory genes and are insulated from the surrounding environment. Here, we report that the p38alpha/beta family of mitogen-activated protein kinases (MAPKs) reversibly regulates the quiescent state of the skeletal muscle satellite cell. Inhibition of p38alpha/beta MAPKs (a) promotes exit from the cell cycle, (b) prevents differentiation, and (c) insulates the cell from most external stimuli allowing the satellite cell to maintain a quiescent state. Activation of satellite cells and p38alpha/beta MAPKs occurs concomitantly, providing further support that these MAPKs function as a molecular switch for satellite cell activation.
Jones
Nathan C
NC
Bayer Corporation, Research Triangle Park, NC 27709, USA.
Tyner
Kristina J
KJ
Nibarger
Lisa
L
Stanley
Heather M
HM
Cornelison
Dawn D W
DD
Fedorov
Yuri V
YV
Olwin
Bradley B
BB
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004789:Enzyme Activation; D020935:MAP Kinase Signaling System; D051379:Mice; D048290:Mitogen-Activated Protein Kinase 11 / Q000378:metabolism*; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism*
D017570:MyoD Protein; D048290:Mitogen-Activated Protein Kinase 11; D048308:Mitogen-Activated Protein Kinase 14; D018995:Myosin Heavy Chains