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秀丽隐杆线虫伴侣蛋白CCT/TRiC是肠道上皮细胞中肌动蛋白和微管蛋白生物合成以及微绒毛形成所必需的。

Caenorhabditis elegans chaperonin CCT/TRiC is required for actin and tubulin biogenesis and microvillus formation in intestinal epithelial cells.

作者信息

Saegusa Keiko, Sato Miyuki, Sato Katsuya, Nakajima-Shimada Junko, Harada Akihiro, Sato Ken

机构信息

Laboratory of Molecular Traffic, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.

Laboratory of Molecular Membrane Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.

出版信息

Mol Biol Cell. 2014 Oct 15;25(20):3095-104. doi: 10.1091/mbc.E13-09-0530. Epub 2014 Aug 20.

Abstract

Intestinal epithelial cells have unique apical membrane structures, known as microvilli, that contain bundles of actin microfilaments. In this study, we report that Caenorhabditis elegans cytosolic chaperonin containing TCP-1 (CCT) is essential for proper formation of microvilli in intestinal cells. In intestinal cells of cct-5(RNAi) animals, a substantial amount of actin is lost from the apical area, forming large aggregates in the cytoplasm, and the apical membrane is deformed into abnormal, bubble-like structures. The length of the intestinal microvilli is decreased in these animals. However, the overall actin protein levels remain relatively unchanged when CCT is depleted. We also found that CCT depletion causes a reduction in the tubulin levels and disorganization of the microtubule network. In contrast, the stability and localization of intermediate filament protein IFB-2, which forms a dense filamentous network underneath the apical surface, appears to be superficially normal in CCT-deficient cells, suggesting substrate specificity of CCT in the folding of filamentous cytoskeletons in vivo. Our findings demonstrate physiological functions of CCT in epithelial cell morphogenesis using whole animals.

摘要

肠道上皮细胞具有独特的顶端膜结构,即微绒毛,其中含有肌动蛋白微丝束。在本研究中,我们报告称,秀丽隐杆线虫中含TCP-1的胞质伴侣蛋白(CCT)对于肠道细胞中微绒毛的正常形成至关重要。在cct-5(RNAi)动物的肠道细胞中,大量肌动蛋白从顶端区域丢失,在细胞质中形成大的聚集体,并且顶端膜变形为异常的泡状结构。这些动物的肠道微绒毛长度缩短。然而,当CCT被耗尽时,总的肌动蛋白水平相对保持不变。我们还发现,CCT的耗尽会导致微管蛋白水平降低以及微管网络紊乱。相比之下,在顶端表面下方形成致密丝状网络的中间丝蛋白IFB-2的稳定性和定位,在CCT缺陷细胞中似乎表面上是正常的,这表明CCT在体内丝状细胞骨架折叠中具有底物特异性。我们的研究结果证明了利用完整动物研究CCT在上皮细胞形态发生中的生理功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f6c/4196862/516b3e684319/3095fig1.jpg

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