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首页> 外文期刊>Nature >Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites
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Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites

机译：自噬通过从中心粒状卫星中去除OFD1来促进原发纤毛发生

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摘要

The primary cilium is a microtubule-based organelle that functions in sensory and signalling pathways. Defects in ciliogenesis can lead to a group of genetic syndromes known as ciliopathies. However, the regulatory mechanisms of primary ciliogenesis in normal and cancer cells are incompletely understood. Here we demonstrate that autophagic degradation of a ciliopathy protein, OFD1 (oral-facial-digital syndrome 1), at centriolar satellites promotes primary cilium biogenesis. Autophagy is a catabolic pathway in which cytosol, damaged organelles and protein aggregates are engulfed in autophagosomes and delivered to lysosomes for destruction. We show that the population of OFD1 at the centriolar satellites is rapidly degraded by autophagy upon serum starvation. In autophagy-deficient Atg5 or Atg3 null mouse embryonic fibroblasts, OFD1 accumulates at centriolar satellites, leading to fewer and shorter primary cilia and a defective recruitment of BBS4 (Bardet-Biedl syndrome 4) to cilia. These defects are fully rescued by OFD1 partial knockdown that reduces the population of OFD1 at centriolar satellites. More strikingly, OFD1 depletion at centriolar satellites promotes cilia formation in both cycling cells and transformed breast cancer MCF7 cells that normally do not form cilia. This work reveals that removal of OFD1 by autophagy at centriolar satellites represents a general mechanism to promote ciliogenesis in mammalian cells. These findings define a newly recognized role of autophagy in organelle biogenesis.
机译：初级纤毛是基于微管的细胞器，在感觉和信号通路中起作用。纤毛发生的缺陷会导致一组遗传综合征，称为纤毛病。但是，对正常细胞和癌细胞中主要纤毛发生的调控机制尚未完全了解。在这里，我们证明了在中心粒卫星处的睫状体蛋白OFD1（口腔数字综合征1）的自噬降解促进了初级纤毛发生。自噬是一种分解代谢途径，其中细胞质，受损的细胞器和蛋白质聚集体被吞噬自噬体吞噬并传递至溶酶体进行破坏。我们显示在中心饥饿的卫星上，ODF1的种群被自噬迅速降解。在自噬缺陷的Atg5或Atg3无效的小鼠胚胎成纤维细胞中，OFD1聚集在中心粒状卫星上，导致越来越少的原发纤毛和BBS4（Bardet-Biedl综合征4）向纤毛的募集缺陷。这些缺陷可以通过OFD1部分击倒得到完全解决，从而减少了中心卫星上OFD1的数量。更令人惊讶的是，中心粒卫星上的OFD1消耗促进了正常细胞不形成纤毛的循环细胞和转化的乳腺癌MCF7细胞中纤毛的形成。这项工作揭示了在中心粒卫星上通过自噬去除OFD1是促进哺乳动物细胞纤毛发生的一般机制。这些发现定义了自噬在细胞器生物发生中的新认识的作用。

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  • 来源
    《Nature》 |2013年第7470期|254-257|共4页
  • 作者

    Zaiming Tang; Mary Grace Lin; Timothy Richard Stowe; She Chen; Muyuan Zhu; Tim Stearns; Brunella Franco; Qing Zhong;

  • 作者单位

    Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA,Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA,Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA,State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058, China;

    Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA;

    Department of Biology, Stanford University, Stanford, California 94305, USA;

    National Institute of Biological Sciences, Beijing 102206, China;

    State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058, China;

    Department of Biology, Stanford University, Stanford, California 94305, USA;

    Medical Genetics Services, Department of Translational Medical Sciences, Federico II University, Via Pietro Castellino 111, Naples, Italy,Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, Naples, Italy;

    Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA,Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA,Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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