A modified UPR stress sensing system reveals a novel tissue distribution of IRE1/XBP1 activity during normal Drosophila development
A modified UPR stress sensing system reveals a novel tissue distribution of IRE1/XBP1 activity during normal Drosophila development
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DOI：
10.1007/s12192-012-0383-x
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发表时间：
2013-05-01
影响因子：
3.8
通讯作者：
Ryoo, Hyung Don
中科院分区：
文献类型：
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作者：
Sone, Michio;Zeng, Xiaomei;Ryoo, Hyung Don
真核细胞通过激活被称为未折叠蛋白反应(UPR)的细胞内信号通路来响应由内质网中未折叠/错误折叠蛋白积累引起的压力。在后生动物中，UPR由三个平行的分支组成，每个分支分别具有其应力感受器蛋白IRE1、ATF6和PERK。在果蝇中，IRE1/XBP1通路被认为是UPR的一个主要分支，但其在正常发育和动态平衡中的生理作用尚不清楚。为了在正常生理条件下观察果蝇组织中IRE1/XBP1的活性，我们修改了以前报道的XBP1应激感应系统(Souid等人，Dev gene Evol 217：159-167,2007；Ryoo等人，EMBO J 26：242-252,2007)，基于最近关于XBP1/HAC1 mRNA非常规剪接的报道(Aragon等人，Nature 457：736-740,2009；Yanagitani等人，Mol Cell 34：191-200,2009；Science 331：586-589,2011)。改进的XBP1应激传感系统使我们能够在三龄幼虫的脑、肠道、马氏管和气管以及成年雄性生殖器官中检测到新的IRE1/XBP1活性。具体地说，在幼虫脑中，IRE1/XBP1活性仅在胶质细胞中检测到，尽管以前的报道主要集中在神经元中的IRE1/XBP1活性。意想不到的胶质细胞IRE1/XBP1活性可能为我们提供新的见解，了解UPR调控的大脑稳态。
Eukaryotic cells respond to stress caused by the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum by activating the intracellular signaling pathways referred to as the unfolded protein response (UPR). In metazoans, UPR consists of three parallel branches, each characterized by its stress sensor protein, IRE1, ATF6, and PERK, respectively. In Drosophila, IRE1/XBP1 pathway is considered to function as a major branch of UPR; however, its physiological roles during the normal development and homeostasis remain poorly understood. To visualize IRE1/XBP1 activity in fly tissues under normal physiological conditions, we modified previously reported XBP1 stress sensing systems (Souid et al., Dev Genes Evol 217: 159-167, 2007; Ryoo et al., EMBO J 26: 242-252, 2007), based on the recent reports regarding the unconventional splicing of XBP1/HAC1 mRNA (Aragon et al., Nature 457: 736-740, 2009; Yanagitani et al., Mol Cell 34: 191-200, 2009; Science 331: 586-589, 2011). The improved XBP1 stress sensing system allowed us to detect new IRE1/XBP1 activities in the brain, gut, Malpighian tubules, and trachea of third instar larvae and in the adult male reproductive organ. Specifically, in the larval brain, IRE1/XBP1 activity was detected exclusively in glia, although previous reports have largely focused on IRE1/XBP1 activity in neurons. Unexpected glial IRE1/XBP1 activity may provide us with novel insights into the brain homeostasis regulated by the UPR.