elipsa is an early determinant of ciliogenesis that links the IFT particle to membrane-associated small GTPase Rab8
elipsa is an early determinant of ciliogenesis that links the IFT particle to membrane-associated small GTPase Rab8
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DOI：
10.1038/ncb1706
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发表时间：
2008-04-01
影响因子：
21.3
通讯作者：
Malicki, Jarema
中科院分区：
文献类型：
--
作者：
Omori, Yoshihiro;Zhao, Chengtian;Malicki, Jarema
纤毛的形成和功能涉及鞭毛内转运（IFT）颗粒在纤毛膜下沿着轴丝微管的运动（1，2）。虽然这一过程已被广泛研究，但其分子基础仍不完全清楚。例如，IFT颗粒如何与跨膜蛋白相互作用是未知的。为了进一步研究IFT颗粒，我们研究了elipsa，这是一个以突变为特征的基因座，该突变导致斑马鱼特别早期的纤毛发生缺陷。我们在这里显示，elipsa编码卷曲螺旋多肽，定位于纤毛。Elipsa蛋白结合到IFT颗粒的组分ift 20，并且秀丽隐杆线虫中的Elipsa同源物DYF-11类似于IFT颗粒在感觉纤毛中移位。这表明Elipsa是IFT颗粒多肽。在斑马鱼胚胎发生的背景下，Elipsa与Rabaptin 5（一种研究充分的内吞作用调节剂）发生遗传相互作用，Rabaptin 5又与Rab 8（一种已知定位于纤毛的小GT酶）发生相互作用。我们发现Rabaptin 5与Elipsa和Rab 8结合，表明这些蛋白质在IFT颗粒和在睫状膜处组装的蛋白质复合物之间提供了桥接机制。
The formation and function of cilia involves the movement of intraflagellar transport ( IFT) particles underneath the ciliary membrane, along axonemal microtubules(1,2). 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.