Gp93, the Drosophila GRP94 ortholog, is required for gut epithelial homeostasis and nutrient assimilation-coupled growth control.
Gp93, the Drosophila GRP94 ortholog, is required for gut epithelial homeostasis and nutrient assimilation-coupled growth control.
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DOI：
10.1016/j.ydbio.2009.12.023
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发表时间：
2010-03-15
影响因子：
2.7
通讯作者：
Nicchitta CV
中科院分区：
文献类型：
--
作者：
Maynard JC;Pham T;Zheng T;Jockheck-Clark A;Rankin HB;Newgard CB;Spana EP;Nicchitta CV
GRP 94，内质网Hsp 90，是一种后生动物限制的伴侣蛋白，对哺乳动物的早期发育至关重要，但对哺乳动物细胞的活力至关重要。这种二分法表明，GRP 94是分泌和/或膜蛋白的功能性表达所必需的，这些蛋白能够使细胞整合到组织中。为了探索这一假说，我们已经确定了果蝇的直系同源物Gp 93，并报告说，Gp 93是果蝇的必需基因。合子Gp 93表达的缺失是晚期幼虫致死的，并导致幼虫中肠（唯一的内胚层来源的幼虫组织）的显著缺陷。Gp 93突变体幼虫显示出明显的缺陷，在中肠上皮细胞，异常铜细胞结构，显着减少肠道酸化，非典型的分隔连接结构，抑制肠道运动，和赤字在肠道营养吸收。Gp 93表达丧失的代谢后果是深远的; Gp 93突变体幼虫表现出饥饿样代谢表型，包括胰岛素信号传导的抑制和氨基酸和甘油三酯的广泛动员。伴随Gp 93表达丧失的铜细胞结构/功能缺陷类似于报道的唇突变（一种铜细胞特化所需的内胚层同源异型基因）和α-血影蛋白突变，从而表明Gp 93在分泌/整合膜蛋白编码的实验室蛋白靶基因和/或整合膜蛋白的功能表达中的重要作用，其与血影蛋白细胞骨架相互作用以赋予上皮细胞膜特化。
GRP94, the endoplasmic reticulum Hsp90, is a metazoan-restricted chaperone essential for early development in mammals, yet dispensable for mammalian cell viability. This dichotomy suggests that GRP94 is required for the functional expression of secretory and/or membrane proteins that enable the integration of cells into tissues. To explore this hypothesis, we have identified the Drosophila ortholog of GRP94, Gp93, and report that Gp93 is an essential gene in Drosophila. Loss of zygotic Gp93 expression is late larval lethal and causes prominent defects in the larval midgut, the sole endoderm-derived larval tissue. Gp93 mutant larvae display pronounced defects in the midgut epithelium, with aberrant copper cell structure, markedly reduced gut acidification, atypical septate junction structure, depressed gut motility, and deficits in intestinal nutrient uptake. The metabolic consequences of the loss of Gp93-expression are profound; Gp93 mutant larvae exhibit a starvation-like metabolic phenotype, including suppression of insulin signaling and extensive mobilization of amino acids and triglycerides. The defects in copper cell structure/function accompanying loss of Gp93 expression resemble those reported for mutations in labial, an endodermal homeotic gene required for copper cell specification, and α-spectrin, thus suggesting an essential role for Gp93 in the functional expression of secretory/integral membrane protein-encoding lab protein target genes and/or integral membrane protein(s) that interact with the spectrin cytoskeleton to confer epithelial membrane specialization.
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影响因子：
64.5
作者：
HASHIMOTO, C;HUDSON, KL;ANDERSON, KV
通讯作者：
ANDERSON, KV
影响因子：
1.9
作者：
Bakker, K.
通讯作者：
Bakker, K.
影响因子：
4.5
作者：
Hull-Thompson J;Muffat J;Sanchez D;Walker DW;Benzer S;Ganfornina MD;Jasper H
通讯作者：
Jasper H
影响因子：
--
作者：
BUTTERWORTH, FM;BODENSTEIN, D;KING, RC
通讯作者：
KING, RC
影响因子：
64.8
作者：
Gutierrez, Eugenio;Wiggins, David;Gould, Alex P.
通讯作者：
Gould, Alex P.