Omori Yoshihiro, Zhao Chengtian, Saras Arunesh, Mukhopadhyay Saikat, Kim Woong, Furukawa Takahisa, Sengupta Piali, Veraksa Alexey, Malicki Jarema
Department of Ophthalmology, Harvard Medical School, MEEI, R513, 243 Charles St. Boston, MA 02114, USA.
Nat Cell Biol. 2008 Apr;10(4):437-44. doi: 10.1038/ncb1706. Epub 2008 Mar 23.
The formation and function of cilia involves the movement of intraflagellar transport (IFT) particles underneath the ciliary membrane, along axonemal microtubules. Although this process has been studied extensively, its molecular basis remains incompletely understood. For example, it is unknown how the IFT particle interacts with transmembrane proteins. To study the IFT particle further, we examined elipsa, a locus characterized by mutations that cause particularly early ciliogenesis defects in zebrafish. We show here that elipsa encodes a coiled-coil polypeptide that localizes to cilia. Elipsa protein binds to Ift20, a component of IFT particles, and Elipsa homologue in Caenorhabditis elegans, DYF-11, translocates in sensory cilia, similarly to the IFT particle. This indicates that Elipsa is an IFT particle polypeptide. In the context of zebrafish embryogenesis, Elipsa interacts genetically with Rabaptin5, a well-studied regulator of endocytosis, which in turn interacts with Rab8, a small GTPase, known to localize to cilia. We show that Rabaptin5 binds to both Elipsa and Rab8, suggesting that these proteins provide a bridging mechanism between the IFT particle and protein complexes that assemble at the ciliary membrane.
纤毛的形成和功能涉及鞭毛内运输（IFT）颗粒在纤毛膜下方沿着轴丝微管的移动。尽管对这一过程已进行了广泛研究，但其分子基础仍未完全明晰。例如，IFT颗粒如何与跨膜蛋白相互作用尚不清楚。为了进一步研究IFT颗粒，我们检测了elipsa，这是一个在斑马鱼中因突变而导致特别早期纤毛发生缺陷的基因座。我们在此表明，elipsa编码一种定位于纤毛的卷曲螺旋多肽。Elipsa蛋白与IFT颗粒的一个组分Ift20结合，并且秀丽隐杆线虫中的Elipsa同源物DYF-11在感觉纤毛中移位，类似于IFT颗粒。这表明Elipsa是一种IFT颗粒多肽。在斑马鱼胚胎发生的背景下，Elipsa与Rabaptin5发生遗传相互作用，Rabaptin5是一种研究充分的内吞作用调节因子，它又与Rab8相互作用，Rab8是一种已知定位于纤毛的小GTP酶。我们表明Rabaptin5与Elipsa和Rab8都结合，这表明这些蛋白在IFT颗粒与在纤毛膜处组装的蛋白复合物之间提供了一种桥梁机制。
