Genetic ablation of afadin causes mislocalization and deformation of Paneth cells in the mouse small intestinal epithelium.
Genetic ablation of afadin causes mislocalization and deformation of Paneth cells in the mouse small intestinal epithelium.
复制标题
阿富丁的遗传消融会导致小鼠小肠上皮中泛细胞的错误定位和变形。
DOI：
10.1371/journal.pone.0110549
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Inoue M
中科院分区：
文献类型：
--
作者：
Tanaka-Okamoto M;Itoh Y;Miyoshi J;Mizoguchi A;Mizutani K;Takai Y;Inoue M
Afadin是一种肌动蛋白亲和结合蛋白，在细胞粘附中与细胞粘附分子nectin协同作用，并以nectin独立的方式与小G蛋白Rap 1定向细胞运动。我们使用afadin条件基因敲除（cKO）小鼠研究了afadin在小肠上皮组织中的作用。Afadin定位于所有类型的上皮细胞在整个隐窝绒毛轴的粘附连接。Paneth细胞位于对照小鼠的隐窝基部，但不局限于此，并迁移到afadin-cKO小鼠的绒毛中。其他类型上皮细胞的分布在突变小鼠中没有显著变化。保留在隐窝中的潘氏细胞表现出异常的形状，被埋在相邻的细胞之间，并且不面向管腔。在这些细胞中，粘附连接和紧密连接的形成受损。Rap 1和EphB 3在对照Paneth细胞中高度表达，但在afadin缺陷Paneth细胞中显著下调。两者合计，结果表明，afadin发挥作用，潘氏细胞的限制性本地化的基础上的隐窝，通过保持其粘附到相邻的隐窝细胞，并抑制他们的运动向绒毛的顶部。
Afadin is an actin filament-binding protein that acts cooperatively in cell adhesion with the cell adhesion molecule nectin, and in directional cell movement with the small G protein Rap1 in a nectin-independent manner. We studied the role of afadin in the organization of the small intestinal epithelium using afadin conditional gene knockout (cKO) mice. Afadin was localized at adherens junctions of all types of epithelial cells throughout the crypt-villus axis. Paneth cells were localized at the base of the crypt in control mice, but not confined there, and migrated into the villi in afadin-cKO mice. The distribution of other types of epithelial cells did not change significantly in the mutant mice. The Paneth cells remaining in the crypt exhibited abnormal shapes, were buried between adjacent cells, and did not face the lumen. In these cells, the formation of adherens junctions and tight junctions was impaired. Rap1 and EphB3 were highly expressed in control Paneth cells but markedly down-regulated in the afadin-deficient Paneth cells. Taken together, the results indicate that afadin plays a role in the restricted localization of Paneth cells at the base of the crypt by maintaining their adhesion to adjacent crypt cells and inhibiting their movement toward the top of villi.
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影响因子：
7.8
作者：
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影响因子：
7.8
作者：
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通讯作者：
Takai, Y
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DOI：
10.1083/jcb.146.5.1117
发表时间：
1999-09-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Takai Y
影响因子：
4
作者：
Miyata, Muneaki;Ogita, Hisakazu;Takai, Yoshimi
通讯作者：
Takai, Yoshimi
影响因子：
4.8
作者：
Hoshino, T;Sakisaka, T;Takai, Y
通讯作者：
Takai, Y