The extracellular and intracellular regions of Crb2a play distinct roles in guiding the formation of the apical zonula adherens
The extracellular and intracellular regions of Crb2a play distinct roles in guiding the formation of the apical zonula adherens
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Crb2a 的细胞外和细胞内区域在引导顶端粘附小带的形成中发挥着不同的作用
DOI：
10.1016/j.biopha.2020.109942
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发表时间：
2020
影响因子：
7.5
通讯作者：
Zou Jian
中科院分区：
文献类型：
--
作者：
Lin Yuchen;Weng Kechao;Liang Jiancheng;Zhou Yao;Hao Qinlong;Hao Yumei;Yao Ke;Zou Jian
跨膜蛋白Crumbs(CRB)是顶端极性的关键调节因子，已知它参与了上皮细胞顶端贴壁的建立，尽管确切的机制仍不清楚。透明带粘附物是维持上皮细胞完整性和有序排列所必需的。小带黏附的丢失会导致上皮源性组织中的形态发生缺陷。在这项研究中，我们发现Crb2a的细胞内尾巴促进了斑马鱼视网膜和晶状体上皮细胞黏附连接(AJs)的顶端分布，但导致组装成不稳定的点状黏附样黏附斑块。Crb2a的胞外区引导AJ由小点粘连向稳定的小带粘连转化。因此，缺少胞外区的截短形式的Crb2a(Crb2aΔex)只能部分修复CRB2全突变斑马鱼(Crb2am289)的视网膜花纹缺陷。相反，Crb2aΔEX的结构性过表达破坏了光感受器外界膜的完整性，光感受器的外界膜来自视网膜神经上皮的带状黏附。这项研究表明，Crb2a的胞外区和胞内区都需要引导顶端粘连带的形成。
The transmembrane protein Crumbs (Crb), a key regulator of apical polarity, has a known involvement in establishment of the apical zonula adherens in epithelia, although the precise mechanism remains elusive. The zonula adherens are required to maintain the integrity and orderly arrangement of epithelia. Loss of the zonula adherens leads to morphogenetic defects in the tissues derived from epithelium. In this study, we revealed that the intracellular tail of Crb2a promoted the apical distribution of adherens junctions (AJs) in zebrafish retinal and lens epithelia, but caused assembly into unstable punctum adherens-like adhesion plaques. The extracellular region of Crb2a guided the transformation of AJs from the punctum adherens into stable zonula adherens. Accordingly, a truncated form of Crb2a lacking the extracellular region (Crb2aΔEX) could only partially rescue the retinal patterning defects incrb2anull mutant zebrafish (crb2am289). By contrast, constitutive over-expression of Crb2aΔEXdisrupted the integrity of the outer limiting membrane in photoreceptors, which is derived from the zonula adherens of the retinal neuroepithelium. This study demonstrated that both the extracellular region and the intracellular tail of Crb2a are required to guide the formation of the apical zonula adherens.