哺乳动物视网膜中Crb蛋白复合体的组成与功能

Composition and function of the Crumbs protein complex in the mammalian retina.

作者信息

Gosens Ilse, den Hollander Anneke I, Cremers Frans P M, Roepman Ronald

机构信息

Department of Human Genetics and Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 10, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.

出版信息

Exp Eye Res. 2008 May;86(5):713-26. doi: 10.1016/j.exer.2008.02.005. Epub 2008 Feb 26.

Abstract

The Crumbs proteins (CRBs) are transmembrane proteins, homologous to Drosophila Crumbs, with a key role in defining the apical membrane domain in photoreceptors as well as in embryonic epithelia. Crumbs proteins are conserved between species and their intracellular domains are involved in organizing a conserved macromolecular protein scaffold with important roles in cell polarity as well as morphogenesis and maintenance of the retina. Mutations in the gene encoding human CRB1, the first one identified out of the three human orthologs, have been associated with a number of retinal dystrophies including Leber amaurosis and retinitis pigmentosa type 12. Although no other mammalian Crumbs complex members as of yet have been associated with retinal degeneration, disruption of different zebrafish and fruitfly orthologs can lead to various retinal defects. The core Crumbs complex localizes apical to the outer limiting membrane, where photoreceptors and Müller glia contact each other. Correct functioning of Crumbs ensures adhesion between these cells by an unknown mechanism. This review summarizes the current view on the composition and function of the Crumbs prsotein complex in the mammalian retina. Recently, a number of new members of the Crumbs protein complex have been identified. These include most members of the membrane palmitoylated protein family (MPP), involved in assembly of macromolecular protein complexes. Some components of the complex are found to exert a function in the photoreceptor synapses and/or at the region of the connecting cilium. Studies using polarized cell cultures or model organisms, like Drosophila and zebrafish, suggest important links of the Crumbs protein complex to several biological processes in the mammalian eye, including retinal patterning, ciliogenesis and vesicular transport.

摘要

“面包屑”蛋白(CRBs)是跨膜蛋白,与果蝇的“面包屑”蛋白同源,在界定光感受器以及胚胎上皮细胞的顶端膜结构域中起关键作用。“面包屑”蛋白在物种间保守,其胞内结构域参与组织一个保守的大分子蛋白支架,该支架在细胞极性以及视网膜的形态发生和维持中发挥重要作用。人类CRB1是三个直系同源基因中最早被鉴定出的,编码该基因的突变与多种视网膜营养不良相关,包括莱伯先天性黑蒙和12型色素性视网膜炎。尽管目前尚未发现其他哺乳动物的“面包屑”复合体成员与视网膜变性有关,但不同斑马鱼和果蝇直系同源基因的破坏会导致各种视网膜缺陷。核心“面包屑”复合体定位于外限制膜的顶端,光感受器和米勒胶质细胞在此处相互接触。“面包屑”的正常功能通过未知机制确保这些细胞之间的黏附。本综述总结了目前关于哺乳动物视网膜中“面包屑”蛋白复合体的组成和功能的观点。最近,已鉴定出“面包屑”蛋白复合体的一些新成员。这些成员包括膜棕榈酰化蛋白家族(MPP)的大多数成员,它们参与大分子蛋白复合体的组装。该复合体的一些组分在光感受器突触和/或连接纤毛区域发挥作用。使用极化细胞培养或果蝇和斑马鱼等模式生物的研究表明,“面包屑”蛋白复合体与哺乳动物眼睛中的几个生物学过程有重要联系,包括视网膜模式形成、纤毛发生和囊泡运输。

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