动纤蛋白运输蛋白 IFT27 通过 GTP 酶 ARL6/BBS3 促进 BBSome 从纤毛中输出。
The intraflagellar transport protein IFT27 promotes BBSome exit from cilia through the GTPase ARL6/BBS3.
机构信息
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
出版信息
Dev Cell. 2014 Nov 10;31(3):265-278. doi: 10.1016/j.devcel.2014.09.004. Epub 2014 Oct 30.
The sorting of signaling receptors into and out of cilia relies on the BBSome, a complex of Bardet-Biedl syndrome (BBS) proteins, and on the intraflagellar transport (IFT) machinery. GTP loading onto the Arf-like GTPase ARL6/BBS3 drives assembly of a membrane-apposed BBSome coat that promotes cargo entry into cilia, yet how and where ARL6 is activated remains elusive. Here, we show that the Rab-like GTPase IFT27/RABL4, a known component of IFT complex B, promotes the exit of BBSome and associated cargoes from cilia. Unbiased proteomics and biochemical reconstitution assays show that, upon disengagement from the rest of IFT-B, IFT27 directly interacts with the nucleotide-free form of ARL6. Furthermore, IFT27 prevents aggregation of nucleotide-free ARL6 in solution. Thus, we propose that IFT27 separates from IFT-B inside cilia to promote ARL6 activation, BBSome coat assembly, and subsequent ciliary exit, mirroring the process by which BBSome mediates cargo entry into cilia.
信号受体在纤毛内外的分拣依赖于 BBSome，这是一种 Bardet-Biedl 综合征 (BBS) 蛋白的复合物，以及内纤毛运输 (IFT) 机制。ARF 样 GTP 酶 ARL6/BBS3 的 GTP 加载驱动与纤毛接近的 BBSome 涂层的组装，促进货物进入纤毛，但 ARL6 如何以及在何处被激活仍然难以捉摸。在这里，我们表明 Rab 样 GTP 酶 IFT27/RABL4，IFT 复合物 B 的已知组成部分，促进 BBSome 和相关货物从纤毛中排出。无偏见的蛋白质组学和生化重构测定表明，在与 IFT-B 的其余部分脱离后，IFT27 直接与非核苷酸形式的 ARL6 相互作用。此外，IFT27 防止非核苷酸形式的 ARL6 在溶液中聚集。因此，我们提出 IFT27 在纤毛内与 IFT-B 分离以促进 ARL6 激活、BBSome 涂层组装和随后的纤毛排出，这反映了 BBSome 介导货物进入纤毛的过程。
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