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可分离的机制驱动秀丽隐杆线虫肠道上皮的局部和全局极性建立。

Separable mechanisms drive local and global polarity establishment in the Caenorhabditiselegans intestinal epithelium.

机构信息

Department of Biology, Stanford University, Stanford, CA 94305, USA.

Department of Biological Sciences, San Jose State University, San Jose, CA 95112, USA.

出版信息

Development. 2022 Nov 15;149(22). doi: 10.1242/dev.200325. Epub 2022 Nov 16.

Abstract

Apico-basolateral polarization is essential for epithelial cells to function as selective barriers and transporters, and to provide mechanical resilience to organs. Epithelial polarity is established locally, within individual cells to establish distinct apical, junctional and basolateral domains, and globally, within a tissue where cells coordinately orient their apico-basolateral axes. Using live imaging of endogenously tagged proteins and tissue-specific protein depletion in the Caenorhabditiselegans embryonic intestine, we found that local and global polarity establishment are temporally and genetically separable. Local polarity is initiated prior to global polarity and is robust to perturbation. PAR-3 is required for global polarization across the intestine but local polarity can arise in its absence, as small groups of cells eventually established polarized domains in PAR-3-depleted intestines in a HMR-1 (E-cadherin)-dependent manner. Despite the role of PAR-3 in localizing PKC-3 to the apical surface, we additionally found that PAR-3 and PKC-3/aPKC have distinct roles in the establishment and maintenance of local and global polarity. Taken together, our results indicate that different mechanisms are required for local and global polarity establishment in vivo.

摘要

顶端-基底极性对于上皮细胞作为选择性屏障和转运体发挥功能,以及为器官提供机械弹性至关重要。上皮极性在个体细胞内局部建立,以建立独特的顶端、连接和基底区域,并在组织内全局建立,使细胞协调其顶端-基底轴的方向。通过对秀丽隐杆线虫胚胎肠内内源标记蛋白的实时成像和组织特异性蛋白耗竭,我们发现局部和全局极性的建立在时间和遗传上是可分离的。局部极性在全局极性之前启动,并且对干扰具有鲁棒性。PAR-3 对于整个肠道的全局极化是必需的,但在其缺失的情况下局部极性也可以出现,因为在 PAR-3 耗尽的肠道中,一小群细胞最终以 HMR-1(E-钙粘蛋白)依赖性方式建立极化区域。尽管 PAR-3 在将 PKC-3 定位到顶端表面中起作用,但我们还发现 PAR-3 和 PKC-3/aPKC 在局部和全局极性的建立和维持中具有不同的作用。总之,我们的结果表明,体内建立局部和全局极性需要不同的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c398/9845746/613aca51cc5b/develop-149-200325-g1.jpg

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