Joubert syndrome Arl13b functions at ciliary membranes and stabilizes protein transport in Caenorhabditis elegans.
Joubert syndrome Arl13b functions at ciliary membranes and stabilizes protein transport in Caenorhabditis elegans.
复制标题
DOI：
10.1083/jcb.200908133
复制
发表时间：
2010-03-22
期刊：
影响因子：
--
通讯作者：
Blacque OE
中科院分区：
文献类型：
--
作者：
Cevik S;Hori Y;Kaplan OI;Kida K;Toivenon T;Foley-Fisher C;Cottell D;Katada T;Kontani K;Blacque OE
小的GTdR Arl 13 b调节纤毛跨膜蛋白定位和顺行IFT组装稳定性。小纤毛G蛋白Arl 13 b是纤毛生物发生和音刺猬信号所需的，并在Joubert综合征（JS）患者中发生突变。在这项研究中，使用秀丽隐杆线虫和哺乳动物细胞培养系统，我们调查了知之甚少的纤毛和Arl 13 b功能的分子基础。首先，我们表明，Arl 13 b/ARL-13的本地化经常被限制到近端睫状体隔室，在那里它与睫状体膜通过棕榈酰化修饰基序。接下来，我们发现功能丧失C。线虫arl-13突变体具有纤毛形态和超微结构缺陷，以及纤毛蛋白定位和转运缺陷;纤毛跨膜蛋白异常积累，PKD-2纤毛丰度升高，并且顺行鞭毛内转运（IFT）不稳定。最后，我们表明，arl-13与其他ciliogenic和纤毛运输相关基因在维持纤毛结构/形态和顺行IFT稳定性的遗传相互作用。总之，这些数据暗示了JS相关的Arl 13 b在睫状膜中的作用，在睫状膜中它调节睫状跨膜蛋白定位和顺行IFT组装稳定性。
The small GTPase Arl13b regulates ciliary transmembrane protein localizations and anterograde IFT assembly stability. The small ciliary G protein Arl13b is required for cilium biogenesis and sonic hedgehog signaling and is mutated in patients with Joubert syndrome (JS). In this study, using Caenorhabditis elegans and mammalian cell culture systems, we investigated the poorly understood ciliary and molecular basis of Arl13b function. First, we show that Arl13b/ARL-13 localization is frequently restricted to a proximal ciliary compartment, where it associates with ciliary membranes via palmitoylation modification motifs. Next, we find that loss-of-function C. elegans arl-13 mutants possess defects in cilium morphology and ultrastructure, as well as defects in ciliary protein localization and transport; ciliary transmembrane proteins abnormally accumulate, PKD-2 ciliary abundance is elevated, and anterograde intraflagellar transport (IFT) is destabilized. Finally, we show that arl-13 interacts genetically with other ciliogenic and ciliary transport–associated genes in maintaining cilium structure/morphology and anterograde IFT stability. Together, these data implicate a role for JS-associated Arl13b at ciliary membranes, where it regulates ciliary transmembrane protein localizations and anterograde IFT assembly stability.
登录
查看更多内容
影响因子：
9.8
作者：
Gorden, Nicholas T.;Arts, Heleen H.;Doherty, Dan
通讯作者：
Doherty, Dan
影响因子：
4.6
作者：
Bae, Young-Kyung;Qin, Hongmin;Barr, Maureen M.
通讯作者：
Barr, Maureen M.
影响因子：
4.8
作者：
Fukata, Yuko;Iwanaga, Tsuyoshi;Fukata, Masaki
通讯作者：
Fukata, Masaki
影响因子：
9.8
作者：
Baala, Lekbir;Romano, Stephane;Attie-Bitach, Tania
通讯作者：
Attie-Bitach, Tania
影响因子：
9.8
作者：
Dixon-Salazar, T;Silhavy, JL;Gleeson, JG
通讯作者：
Gleeson, JG