Sphingomyelin Levels in the Plasma Membrane Correlate with the Activation State of Muscle Satellite Cells
Yosuke Nagata 1, Hideshi Kobayashi 1, Masato Umeda 1, Naoshi Ohta 1, Seiichiro Kawashima 1, Peter S. Zammit 1 and Ryoichi Matsuda 1*
1 Department of Life Sciences, The University of Tokyo, Tokyo, Japan (YN,RM); Muscle Cell Biology Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, London, United Kingdom (YN,PSZ); Department of Molecular Biodynamics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan (HK,MU); Research Laboratory, Zenyaku Kogyo Co. Ltd., Tokyo, Japan (NO,SK)
* To whom correspondence should be addressed. E-mail: cmatsuda{at}mail.ecc.u-tokyo.ac.jp.
Submitted on March 2, 2005
Accepted on 14 September 2005
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Abstract |
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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. Upon activation, however, the levels of sphingomyelin drop, so that lysenin did not label proliferating satellite cells. While most satellite cell progeny differentiate, others stop cycling, maintain Pax7, down-regulate MyoD and escape immediate differentiation. Importantly, many of these Pax7+ve/MyoD-ve cells also re-gained lysenin binding on their surface, showing that the levels of sphingomyelin had again increased. Together, 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.
Key Words:
satellite cell, stem cell, skeletal muscle, activation, regeneration, sphingolipid, sphingomyelin, lysenin