Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China; The Institute of Translational Medicine, Zhejiang University, Hangzhou, 310058, China.
Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China; Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, 310009, China.
Biomed Pharmacother. 2020 May;125:109942. doi: 10.1016/j.biopha.2020.109942. Epub 2020 Feb 7.
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 (Crb2a) could only partially rescue the retinal patterning defects in crb2a null mutant zebrafish (crb2a). By contrast, constitutive over-expression of Crb2a disrupted 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.
跨膜蛋白 Crumbs（Crb）是顶端极性的关键调节因子，已知其参与上皮细胞顶端粘着带的形成，尽管其确切机制仍不清楚。粘着带对于维持上皮细胞的完整性和有序排列是必需的。粘着带的丧失会导致来源于上皮的组织发生形态发生缺陷。在这项研究中，我们揭示了 Crb2a 的细胞内尾部促进了斑马鱼视网膜和晶状体上皮细胞中粘着斑的顶端分布，但导致粘着斑形成不稳定的点状粘着斑样粘附斑。Crb2a 的细胞外区域指导粘着斑从点状粘着斑向稳定的粘着带的转变。因此，缺乏细胞外区域的 Crb2a 截短形式（Crb2a）只能部分挽救 crb2a 缺失突变体斑马鱼（crb2a）的视网膜图案缺陷。相比之下，Crb2a 的组成性过表达破坏了光感受器的外节限膜的完整性，该膜来源于视网膜神经上皮的粘着带。这项研究表明，Crb2a 的细胞外区域和细胞内尾部都需要引导顶端粘着带的形成。
