Sphingomyelin levels in the plasma membrane correlate with the activation state of muscle satellite cells.
Satellite cells are responsible for postnatal growth, hypertrophy, and regeneration of skeletal muscle. They are normally quiescent, and must be activated to fulfill these functions, yet little is known of how this is regulated. As a first step in determining the role of lipids in this process, we examined the dynamics of sphingomyelin in the plasma membrane. Sphingomyelin contributes to caveolae/lipid rafts, which act to concentrate signaling molecules, and is also a precursor of several bioactive lipids. Proliferating or differentiated C2C12 muscle cells did not bind lysenin, a sphingomyelin-specific binding protein, but noncycling reserve cells did. Quiescent satellite cells also bound lysenin, revealing high levels of sphingomyelin in their plasma membranes. On activation, however, the levels of sphingomyelin drop, so that lysenin did not label proliferating satellite cells. Although most satellite cell progeny differentiate, others stop cycling, maintain Pax7, downregulate MyoD, and escape immediate differentiation. Importantly, many of these Pax7-positive/MyoD-negative cells also regained lysenin binding on their surface, showing that the levels of sphingomyelin had again increased. Our observations show that quiescent satellite cells are characterized by high levels of sphingomyelin in their plasma membranes and that lysenin provides a novel marker of myogenic quiescence.
Nagata
Yosuke
Y
Department of Life Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan.
Kobayashi
Hideshi
H
Umeda
Masato
M
Ohta
Naoshi
N
Kawashima
Seiichiro
S
Zammit
Peter S
PS
Matsuda
Ryoichi
R
D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D011506:Proteins / Q000737:chemistry; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D013109:Sphingomyelins / Q000737:chemistry / Q000378:metabolism*; D014118:Toxins, Biological
D007202:Indicators and Reagents; D011506:Proteins; D013109:Sphingomyelins; D014118:Toxins, Biological; C107040:lysenin