Imbalances in endoplasmic reticulum (ER) homeostasis provoke a condition known as ER stress and activate the unfolded protein response (UPR) pathway, an evolutionarily conserved cell survival mechanism. Here, we show that mouse myoblasts respond to UPR activation by stimulating glycogenesis and the formation of α-amylase-degradable, glycogen-containing ER structures. We demonstrate that the glycogen-binding protein Stbd1 is markedly upregulated through the PERK signalling branch of the UPR pathway and is required for the build-up of glycogen structures in response to ER stress activation. In the absence of ER stress, Stbd1 overexpression is sufficient to induce glycogen clustering but does not stimulate glycogenesis. Glycogen structures induced by ER stress are degraded under conditions of glucose restriction through a process that does not depend on autophagosome–lysosome fusion. Furthermore, we provide evidence that failure to induce glycogen clustering during ER stress is associated with enhanced activation of the apoptotic pathway. Our results reveal a so far unknown response of mouse myoblasts to ER stress and uncover a novel specific function of Stbd1 in this process, which may have physiological implications during myogenic differentiation.

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内质网 (ER) 稳态失衡会引发一种称为 ER 应激的状况，并激活未折叠蛋白反应 (UPR) 途径，这是一种进化上保守的细胞生存机制。在这里，我们发现小鼠成肌细胞通过刺激糖原生成和α-淀粉酶可降解的、含糖原的内质网结构的形成来响应 UPR 激活。我们证明，糖原结合蛋白 Stbd1 通过 UPR 通路的 PERK 信号分支显着上调，并且是响应 ER 应激激活而构建糖原结构所必需的。在没有 ER 应激的情况下，Stbd1 过表达足以诱导糖原聚集，但不会刺激糖原生成。内质网应激诱导的糖原结构在葡萄糖限制条件下通过不依赖自噬体-溶酶体融合的过程降解。此外，我们提供的证据表明，在内质网应激期间未能诱导糖原聚集与细胞凋亡途径的增强激活有关。我们的结果揭示了小鼠成肌细胞对 ER 应激的迄今为止未知的反应，并揭示了 Stbd1 在此过程中的一种新的特定功能，这可能在生肌分化过程中具有生理意义。

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