Caenorhabditis elegans chaperonin CCT/TRiC is required for actin and tubulin biogenesis and microvillus formation in intestinal epithelial cells.
Caenorhabditis elegans chaperonin CCT/TRiC is required for actin and tubulin biogenesis and microvillus formation in intestinal epithelial cells.
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秀丽隐杆线虫伴侣蛋白 CCT/TRiC 是肠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。
DOI：
10.1091/mbc.e13-09-0530
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发表时间：
2014-10-15
影响因子：
3.3
通讯作者：
Sato K
中科院分区：
文献类型：
--
作者：
Saegusa K;Sato M;Sato K;Nakajima-Shimada J;Harada A;Sato K
秀丽隐杆线虫伴侣蛋白CCT是肌动蛋白和微管蛋白生物合成所必需的，因此对于肠细胞中微绒毛的形成是必需的。CCT/TRiC的缺失对中间丝蛋白IFB-2或细胞骨架连接蛋白ERM-1没有强烈的影响，表明CCT/TRiC在活体动物中表现出明显的底物特异性。肠上皮细胞具有独特的顶端膜结构，称为微绒毛，含有成束的肌动蛋白微丝。在这项研究中，我们报告，秀丽隐杆线虫胞质伴侣蛋白含有TCP-1（CCT）是必不可少的适当形成微绒毛在肠细胞。在cct-5（RNAi）动物的肠细胞中，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气泡样结构。这些动物的肠微绒毛长度减少。然而，当CCT耗尽时，整体肌动蛋白水平保持相对不变。我们还发现，CCT耗竭导致微管蛋白水平的降低和微管网络的解体。相比之下，稳定性和定位的中间丝蛋白IFB-2，它形成了一个致密的丝状网络下的顶端表面，似乎是表面上正常的CCT缺陷的细胞，表明底物特异性的CCT在体内丝状细胞骨架的折叠。我们的研究结果证明了CCT在上皮细胞形态发生中的生理功能。
Caenorhabditis elegans chaperonin CCT is required for the biogenesis of actin and tubulin and is thereby essential for microvillus formation in intestinal cells. Loss of CCT/TRiC had no strong effects on intermediate filament protein IFB-2 or cytoskeletal linker protein ERM-1, suggesting that CCT/TRiC exhibits clear substrate specificity in living animals. 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.