Sphingomyelin levels in the plasma membrane correlate with the activation state of muscle satellite cells
Sphingomyelin levels in the plasma membrane correlate with the activation state of muscle satellite cells
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DOI：
10.1369/jhc.5a6675.2006
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发表时间：
2006-04-01
影响因子：
3.2
通讯作者：
Matsuda, R
中科院分区：
文献类型：
--
作者：
Nagata, Y;Kobayashi, H;Matsuda, R
卫星细胞负责骨骼肌的出生后生长、肥大和再生。它们通常是静止的，必须被激活才能实现这些功能，但人们对它是如何调节的知之甚少。作为确定脂质在这一过程中的作用的第一步，我们研究了鞘磷脂在质膜中的动力学。鞘磷脂有助于小窝/脂筏，其作用是浓缩信号分子，并且也是几种生物活性脂质的前体。再生或分化的C2 C12肌细胞不结合胞溶素，鞘磷脂特异性结合蛋白，但非循环储备细胞。静止的卫星细胞也结合胞溶素，揭示了其质膜中高水平的鞘磷脂。然而，在激活时，鞘磷脂的水平下降，因此胞溶素不能标记增殖的卫星细胞。虽然大多数卫星细胞后代分化，其他停止循环，保持Pax 7，下调MyoD，逃避立即分化。重要的是，许多这些Pax 7阳性/MyoD阴性细胞也恢复了其表面上的胞溶素结合，表明鞘磷脂的水平再次增加。我们的观察结果表明，静止卫星细胞的特征在于其质膜中高水平的鞘磷脂，并且胞溶素提供了肌源性静止的新标记。
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.