Bulgakova Natalia A, Knust Elisabeth
Max-Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, Dresden, Germany.
J Cell Sci. 2009 Aug 1;122(Pt 15):2587-96. doi: 10.1242/jcs.023648.
The evolutionarily conserved Crumbs protein complex is a key regulator of cell polarity and cell shape in both invertebrates and vertebrates. The important role of this complex in normal cell function is illustrated by the finding that mutations in one of its components, Crumbs, are associated with retinal degeneration in humans, mice and flies. Recent results suggest that the Crumbs complex plays a role in the development of other disease processes that are based on epithelial dysfunction, such as tumorigenesis or the formation of cystic kidneys. Localisation of the complex is restricted to a distinct region of the apical plasma membrane that abuts the zonula adherens in epithelia and photoreceptor cells of invertebrates and vertebrates, including humans. In addition to the core components, a variety of other proteins can be recruited to the complex, depending on the cell type and/or developmental stage. Together with diverse post-transcriptional and post-translational mechanisms that regulate the individual components, this provides an enormous functional diversity and flexibility of the complex. In this Commentary, we summarise findings concerning the organisation and modification of the Crumbs complex, and the conservation of its constituents from flies to mammals. In addition, we discuss recent results that suggest its participation in various human diseases, including blindness and tumour formation.
进化上保守的Crumbs蛋白复合体是无脊椎动物和脊椎动物中细胞极性和细胞形状的关键调节因子。该复合体在正常细胞功能中的重要作用体现在其一个组成部分Crumbs的突变与人类、小鼠和果蝇的视网膜变性有关这一发现中。最近的研究结果表明，Crumbs复合体在基于上皮功能障碍的其他疾病过程的发展中发挥作用，如肿瘤发生或多囊肾的形成。该复合体的定位局限于顶端质膜的一个特定区域，该区域与无脊椎动物和脊椎动物（包括人类）上皮细胞和光感受器细胞中的紧密连接相邻。除了核心成分外，根据细胞类型和/或发育阶段，还可以招募多种其他蛋白质到该复合体中。与调节各个成分的多种转录后和翻译后机制一起，这为该复合体提供了巨大的功能多样性和灵活性。在这篇评论中，我们总结了关于Crumbs复合体的组织和修饰及其成分从果蝇到哺乳动物的保守性的研究结果。此外，我们还讨论了最近的研究结果，这些结果表明它参与了包括失明和肿瘤形成在内的各种人类疾病。
