Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6346-51. doi: 10.1073/pnas.1002401107. Epub 2010 Mar 22.
Primary cilia are microtubule-based membrane projections located at the surface of many cells. Defects in primary cilia formation have been implicated in a number of genetic disorders, such as Bardet-Biedl Syndrome and Polycystic Kidney Disease. Recent studies have demonstrated that polarized vesicular transport involving Rab8 and its guanine nucleotide-exchange factor Rabin8 is essential for primary ciliogenesis. Here we report that Rabin8 is a direct downstream effector of Rab11, which functions in membrane trafficking from the trans-Golgi network and recycling endosomes. Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8. Rab11 is enriched at the base of the primary cilia and inhibition of Rab11 function by a dominant-negative mutant or RNA interference blocks primary ciliogenesis. Our results suggest that Rab GTPases coordinate with each other in the regulation of vesicular trafficking during primary ciliogenesis.
原发性纤毛是位于许多细胞表面的基于微管的膜突起。原发性纤毛形成缺陷与许多遗传疾病有关，如 Bardet-Biedl 综合征和多囊肾病。最近的研究表明，涉及 Rab8 和其鸟嘌呤核苷酸交换因子 Rabin8 的极化囊泡运输对于原发性纤毛发生是必不可少的。在这里，我们报告 Rabin8 是 Rab11 的直接下游效应物，Rab11 在从 Trans-Golgi 网络和再循环内体的膜运输中起作用。以 GTP 结合形式存在的 Rab11 与 Rabin8 相互作用，并在动力学上刺激 Rabin8 对 Rab8 的鸟嘌呤核苷酸交换活性。Rab11 在原发性纤毛的基部富集，并且通过显性负突变体或 RNA 干扰抑制 Rab11 功能会阻止原发性纤毛发生。我们的结果表明，Rab GTPases 在原发性纤毛发生过程中相互协调以调节囊泡运输。
