The novel centriolar satellite protein SSX2IP targets Cep290 to the ciliary transition zone
The novel centriolar satellite protein SSX2IP targets Cep290 to the ciliary transition zone
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DOI：
10.1091/mbc.e13-09-0526
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发表时间：
2014-02-15
影响因子：
3.3
通讯作者：
Gruss, Oliver J.
中科院分区：
文献类型：
--
作者：
Klinger, Maren;Wang, Wenbo;Gruss, Oliver J.
在分化的人类细胞中，初级纤毛完成将机械或化学刺激转化为细胞内信号的基本功能。纤毛的形成和维持需要与中心粒衍生的基体相关的多种功能，轴丝微管从所述基体生长并且组装门以维持特定的纤毛蛋白质组。在这里，我们描述了一种新的中心粒卫星蛋白，滑膜肉瘤X断裂点相互作用蛋白2（SSX2IP），在初级纤毛组装的功能。我们发现，SSX2IP定位于人体和小鼠纤毛细胞的初级纤毛基体。在人类细胞中使用小干扰RNA敲低，我们证明了SSX2IP对纤毛病相关卫星蛋白Cep290有效招募到卫星和基体的重要性。Cep290在将蛋白质门控至睫状体隔室中起核心作用。与此相一致，SSX2IP的丢失大大减少了BBSome的进入，BBSome的功能是将膜蛋白靶向初级纤毛，并干扰了纤毛膜蛋白靶向的关键调节因子Rab8的有效积累。最后，我们表明SSX2IP敲低限制了睫状膜蛋白和BBSome货物，生长抑素受体3的靶向，并显着降低轴丝长度。我们的数据建立SSX2IP作为一种新的睫状膜蛋白与Cep290，BBSome，Rab8合作的靶向因子。
In differentiated human cells, primary cilia fulfill essential functions in converting mechanical or chemical stimuli into intracellular signals. Formation and maintenance of cilia require multiple functions associated with the centriole-derived basal body, from which axonemal microtubules grow and which assembles a gate to maintain the specific ciliary proteome. Here we characterize the function of a novel centriolar satellite protein, synovial sarcoma X breakpoint-interacting protein 2 (SSX2IP), in the assembly of primary cilia. We show that SSX2IP localizes to the basal body of primary cilia in human and murine ciliated cells. Using small interfering RNA knockdown in human cells, we demonstrate the importance of SSX2IP for efficient recruitment of the ciliopathy-associated satellite protein Cep290 to both satellites and the basal body. Cep290 takes a central role in gating proteins to the ciliary compartment. Consistent with that, loss of SSX2IP drastically reduces entry of the BBSome, which functions to target membrane proteins to primary cilia, and interferes with efficient accumulation of the key regulator of ciliary membrane protein targeting, Rab8. Finally, we show that SSX2IP knockdown limits targeting of the ciliary membrane protein and BBSome cargo, somatostatin receptor 3, and significantly reduces axoneme length. Our data establish SSX2IP as a novel targeting factor for ciliary membrane proteins cooperating with Cep290, the BBSome, and Rab8.