Sphingomyelin Levels in the Plasma Membrane Correlate with the Activation State of Muscle Satellite Cells

Abstract

S U M M A R Y 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. (J Histochem Cytochem 54:375-384, 2006)

Pax7 and myogenic progression in skeletal muscle satellite cells

“…Quiescent satellite cells express the paired box transcription factor family member Pax7 (Seale et al, 2000). When activated, they coexpress Pax7 with MyoD (Grounds et al, 1992;Yablonka-Reuveni and Rivera, 1994;Zammit et al, 2002), a key transcription factor for myogenic differentiation and a member of the myogenic regulatory factor (MRFs) family, comprising MyoD, Myf5, myogenin and Mrf4 (reviewed by Tajbakhsh and Buckingham, 2000 (Zammit et al, 2004;Nagata et al, 2006). A similar mechanism has also been described during muscle growth in chicken (Halevy et al, 2004).…”

Functional interaction between TRPC1 channel and connexin-43 protein: a novel pathway underlying S1P action on skeletal myogenesis

“…Its role in skeletal muscle cell biology is beginning to be highlighted by recent data showing that the sphingolipid is able to promote satellite cell activation and proliferation [2,3], regulate myogenic differentiation [4][5][6], and exert a trophic action on denervated muscle [7]. S1P actions on skeletal myoblast differentiation are strictly dependent on intracellular Ca 2?…”

Formoterol May Activate Rat Muscle Regeneration During Cancer Cachexia

“…When they proliferate, the levels of Pax7 decrease and other molecules involved in differentiation (such as myogenin) increase their expression. There is a part of the proliferating population that maintains the levels of Pax7, but not of MyoD, which returns to their state of quiescence [34][35][36] . Thus, as shown in Table 1 tumour burden actually decreases Pax-7, MyoD and myogenin mRNA expression.…”