Division of Craniofacial and Molecular Genetics, and Program in Genetics, Sackler School of Graduate Biomedical Studies, Tufts University, Boston, MA, USA.
EMBO J. 2011 May 20;30(13):2532-44. doi: 10.1038/emboj.2011.165.
Cilia are required for the development and function of many organs. Efficient transport of protein cargo along ciliary axoneme is necessary to sustain these processes. Despite its importance, the mode of interaction between the intraflagellar ciliary transport (IFT) mechanism and its cargo proteins remains poorly understood. Our studies demonstrate that IFT particle components, and a Meckel-Gruber syndrome 1 (MKS1)-related, B9 domain protein, B9d2, bind each other and contribute to the ciliary localization of Inversin (Nephrocystin 2). B9d2, Inversin, and Nephrocystin 5 support, in turn, the transport of a cargo protein, Opsin, but not another photoreceptor ciliary transmembrane protein, Peripherin. Interestingly, the components of this mechanism also contribute to the formation of planar cell polarity in mechanosensory epithelia. These studies reveal a molecular mechanism that mediates the transport of selected ciliary cargos and is of fundamental importance for the differentiation and survival of sensory cells.
纤毛对于许多器官的发育和功能都是必需的。为了维持这些过程，蛋白货物沿着纤毛轴丝的有效运输是必需的。尽管其重要性，但是内鞭毛运输（IFT）机制与其货物蛋白之间的相互作用模式仍然知之甚少。我们的研究表明，IFT 颗粒成分和一个 Meckel-Gruber 综合征 1（MKS1）相关的 B9 结构域蛋白 B9d2 相互结合，并有助于反向蛋白（多囊肾病蛋白 2）的纤毛定位。反过来，B9d2、反向蛋白和多囊肾病蛋白 5 又支持货物蛋白视蛋白的运输，但不支持另一种光感受器纤毛跨膜蛋白外周蛋白。有趣的是，该机制的成分也有助于机械敏感上皮的平面细胞极性的形成。这些研究揭示了一种分子机制，介导了选定的纤毛货物的运输，对于感觉细胞的分化和存活至关重要。
