The requirement of IRE1 and XBP1 in resolving physiological stress during Drosophila development.
The requirement of IRE1 and XBP1 in resolving physiological stress during Drosophila development.
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DOI：
10.1242/jcs.203612
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发表时间：
2017-09-15
影响因子：
4
通讯作者：
Ryoo HD
中科院分区：
文献类型：
--
作者：
Huang HW;Zeng X;Rhim T;Ron D;Ryoo HD
IRE 1介导未折叠蛋白反应（UPR），部分通过调节响应内质网（ER）应激的XBP 1 mRNA剪接。在培养的后生动物细胞中，IRE 1也表现出不依赖于XBP 1的生物化学活性。IRE 1和XBP 1是果蝇和哺乳动物中发育必需的基因，但生理性ER应激的来源以及XBP 1激活相对于其他IRE 1功能对发育的相对贡献仍然未知。在这里，我们用果蝇来解决这个问题。我们发现，发育中的消化道、脂肪体和男性生殖器官的特定区域是生理应激的来源，需要Ire 1和Xbp 1来解决。特别是，与Xbp 1无效突变相关的发育致死性通过Xbp 1在消化道中的转基因表达来挽救。IRE 1的结构域参与检测未折叠的蛋白质，切割RNA和激活XBP 1剪接都是发育所必需的。Ire 1突变体幼虫中的发育缺陷的早期发作相比，在Xbp 1-null苍蝇支持的发展作用，XBP 1独立的IRE 1 RNA酶活性，同时挑战的重要性，RNA酶独立的效应机制的果蝇IRE 1功能。摘要：应激反应蛋白IRE 1和XBP 1在后生动物中是发育必需的。我们确定了果蝇生理应激的来源，并确定了应激反应信号的分子要求。
IRE1 mediates the unfolded protein response (UPR) in part by regulating XBP1 mRNA splicing in response to endoplasmic reticulum (ER) stress. In cultured metazoan cells, IRE1 also exhibits XBP1-independent biochemical activities. IRE1 and XBP1 are developmentally essential genes in Drosophila and mammals, but the source of the physiological ER stress and the relative contributions of XBP1 activation versus other IRE1 functions to development remain unknown. Here, we employed Drosophila to address this question. Explicitly, we find that specific regions of the developing alimentary canal, fat body and the male reproductive organ are the sources of physiological stress that require Ire1 and Xbp1 for resolution. In particular, the developmental lethality associated with an Xbp1 null mutation was rescued by transgenic expression of Xbp1 in the alimentary canal. The domains of IRE1 that are involved in detecting unfolded proteins, cleaving RNAs and activating XBP1 splicing were all essential for development. The earlier onset of developmental defects in Ire1 mutant larvae compared to in Xbp1-null flies supports a developmental role for XBP1-independent IRE1 RNase activity, while challenging the importance of RNase-independent effector mechanisms of Drosophila IRE1 function. Summary: The stress-response proteins IRE1 and XBP1 are developmentally essential in metazoans. We identify the source of the physiological stress in Drosophila and determine the molecular requirements for stress response signaling.
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影响因子：
11.4
作者：
Lee, AH;Chu, GC;Glimcher, LH
通讯作者：
Glimcher, LH
影响因子：
11.4
作者：
Ferrandon, D;Jung, AC;Hoffmann, JA
通讯作者：
Hoffmann, JA
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16
作者：
Hedengren, M;Åsling, B;Hultmark, D
通讯作者：
Hultmark, D
影响因子：
64.5
作者：
Lee, Kenneth P. K.;Dey, Madhusudan;Sicheri, Frank
通讯作者：
Sicheri, Frank