ER Stress in Pancreatic β Cells: The Thin Red Line Between Adaptation and Failure
ER Stress in Pancreatic β Cells: The Thin Red Line Between Adaptation and Failure
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DOI：
10.1126/scisignal.3110pe7
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发表时间：
2010-02-23
影响因子：
7.3
通讯作者：
Cnop, Miriam
中科院分区：
文献类型：
--
作者：
Eizirik, Decio L.;Cnop, Miriam
分泌细胞，如胰腺β细胞，在急性或慢性刺激期间面临增加蛋白质合成数倍的挑战。这对内质网（ER）造成了负担，内质网是胰岛素原合成和折叠发生的细胞器。因此，β细胞使用各种适应性机制来调节ER的功能能力以满足主要需求。这些检查和平衡机制统称为未折叠蛋白质反应（UPR）。目前还不清楚UPR信号最终是如何调节的，以及生理和病理反应之间的界限是什么。新的发现指出急性和慢性代谢通量和化学ER应激源对UPR换能器，支架蛋白和磷酸酶之间形成复合物的不同影响。这些调查结果和其他调查结果首次揭示了不同的信号是如何触发普遍定期审议结果的。
Secretory cells, such as pancreatic beta cells, face the challenge of increasing protein synthesis severalfold during acute or chronic stimulation. This poses a burden on the endoplasmic reticulum (ER), the organelle where proinsulin synthesis and folding takes place. Thus, beta cells use various adaptive mechanisms to adjust the functional capacity of the ER to the prevailing demand. These check-and-balance mechanisms are collectively known as the unfolded protein response (UPR). It remains unclear how UPR signaling is ultimately regulated and what delineates the boundaries between a physiological and a pathological response. New discoveries point to the divergent effects of acute and chronic metabolic fluxes and chemical ER stressors on the formation of complexes among UPR transducers, scaffold proteins, and phosphatases. These and other findings provide a first glimpse on how different signals trigger diverging UPR outcomes.