可分离机制驱动秀丽隐杆线虫肠道上皮的局部和全局极性建立

M. Pickett, M. Sallee, Victor F. Naturale, Deniz Akpinaroglu, Joo Lee, K. Shen, J. Feldman
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引用次数: 8

摘要

顶基底侧极化是上皮细胞作为选择性屏障和转运体以及为器官提供机械弹性所必需的。上皮极性是局部建立的,在单个细胞内建立不同的顶端、连接和基底外侧结构域,而在组织内,细胞协调地定位其顶端-基底外侧轴。通过对秀丽隐杆线虫胚胎肠内内源性标记蛋白和组织特异性蛋白消耗的实时成像,我们发现局部和全局极性的建立在时间和基因上是可分离的。局部极性先于全局极性产生,对扰动具有鲁棒性。PAR-3对于整个肠道的极化是必需的,但对于局部极性的建立不是必需的,因为一小群细胞能够以HMR-1/ e -钙粘蛋白依赖的方式在PAR-3缺失的肠道中正确地建立极化结构域。par3和PKC-3/aPKC虽然属于相同的顶端蛋白复合体,但在局部和全局极性的建立和维持中具有不同的作用。总之,我们的研究结果表明,体内局部和全局极性的建立需要不同的机制。活体成像和肠道特异性蛋白耗竭显示,顶端-基底侧极性的建立可以在单个细胞的局部水平和整个组织的整体水平上暂时和遗传上分离。
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Separable mechanisms drive local and global polarity establishment in the Caenorhabditis elegans intestinal epithelium
Apico-basolateral polarization is essential for epithelial cells to function as selective barriers and transporters, and to provide mechanical resiliency 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 C. elegans 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 is not required for local polarity establishment as small groups of cells are able to correctly establish polarized domains in PAR-3 depleted intestines in an HMR-1/E-cadherin dependent manner. Despite belonging to the same apical protein complex, we additionally find that PAR-3 and PKC-3/aPKC have distinct roles in the establishment and maintenance of local and global polarity. Together, our results indicate that different mechanisms are required for local and global polarity establishment in vivo. SUMMARY STATEMENT Live-imaging and intestine specific protein depletion reveal that apico-basolateral polarity establishment can be temporally and genetically separated at the local level of individual cells and globally, across a tissue.
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