Transient Ca2+ depletion from the endoplasmic reticulum is critical for skeletal myoblast differentiation
Transient Ca2+ depletion from the endoplasmic reticulum is critical for skeletal myoblast differentiation
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DOI：
10.1096/fj.14-261529
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发表时间：
2015-05-01
期刊：
影响因子：
4.8
通讯作者：
Morishima, Nobuhiro
中科院分区：
文献类型：
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作者：
Nakanishi, Keiko;Kakiguchi, Kisa;Morishima, Nobuhiro
内质网 (ER) 应激是一种细胞状况，由于各种但特定的原因，未折叠的蛋白质在内质网中积聚。生理性内质网应激在成肌细胞分化过程中短暂发生，尽管其原因尚不清楚，但它在肌纤维形成中发挥着关键作用。为了研究内质网应激的机制，我们监测了小鼠成肌细胞分化过程中的内质网形态。在体外和体内成肌细胞融合之前，新的内质网衍生结构短暂出现。电子显微镜研究表明，这些结构由具有狭窄内腔的假同心内质网池组成。通过药理学诱导的 ER Ca2+ 耗竭以及分化成肌细胞中 ER Ca2+ 流出通道的抑制而特异形成的类似结构显着抑制了 ER 特异性变形和 ER 应激信号传导。因此，我们将这种新结构命名为钙消耗应激激活反应（SARC）体。在 SARC 体形成之前，基质相互作用分子 1 (STIM1)（一种 ER Ca2+ 传感器蛋白）形成 ER Ca2+ 耗竭特异性簇。此外，由成肌细胞融合所表现的成肌细胞分化在与抑制ER Ca2+耗竭相同的条件下并不进行。总而言之，这些观察结果表明 ER Ca2+ 耗竭是成肌细胞融合的先决条件，导致生理性 ER 应激信号传导和 SARC 体形成。Nakanishi, K.、Kakiguchi, K.、Yonemura, S.、Nakano, A.、Morishima, N. 内质网的瞬时 Ca2+ 耗竭对于骨骼肌成肌细胞分化至关重要。
Endoplasmic reticulum (ER) stress is a cellular condition in which unfolded proteins accumulate in the ER because of various but specific causes. Physiologic ER stress occurs transiently during myoblast differentiation, and although its cause remains unknown, it plays a critical role in myofiber formation. To examine the mechanism underlying ER stress, we monitored ER morphology during differentiation of murine myoblasts. Novel ER-derived structures transiently appeared prior to myoblast fusion both in vitro and in vivo. Electron microscopy studies revealed that these structures consisted of pseudoconcentric ER cisternae with narrow lumens. Similar structures specifically formed by pharmacologically induced ER Ca2+ depletion, and inhibition of ER Ca2+ efflux channels in differentiating myoblasts considerably suppressed ER-specific deformation and ER stress signaling. Thus, we named the novel structures stress-activated response to Ca2+ depletion (SARC) bodies. Prior to SARC body formation, stromal interaction molecule 1 (STIM1), an ER Ca2+ sensor protein, formed ER Ca2+ depletion-specific clusters. Furthermore, myoblast differentiation manifested by myoblast fusion did not proceed under the same conditions as inhibition of ER Ca2+ depletion. Altogether, these observations suggest that ER Ca2+ depletion is a prerequisite for myoblast fusion, causing both physiologic ER stress signaling and SARC body formation.Nakanishi, K., Kakiguchi, K., Yonemura, S., Nakano, A., Morishima, N. Transient Ca2+ depletion from the endoplasmic reticulum is critical for skeletal myoblast differentiation.