دورية أكاديمية

Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites.

التفاصيل البيبلوغرافية
العنوان: Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites.
المؤلفون: Tang Z; Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA., Lin MG, Stowe TR, Chen S, Zhu M, Stearns T, Franco B, Zhong Q
المصدر: Nature [Nature] 2013 Oct 10; Vol. 502 (7470), pp. 254-7. Date of Electronic Publication: 2013 Oct 02.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة: Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH: Autophagy*/genetics, Centrioles/*metabolism , Cilia/*physiology , Proteins/*metabolism, Animals ; Cell Line ; Cilia/genetics ; Cilia/metabolism ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; MCF-7 Cells ; Mice ; Protein Transport ; Proteins/genetics
مستخلص: 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.
التعليقات: Comment in: Nature. 2013 Oct 10;502(7470):180-1. (PMID: 24089206)
Comment in: Nat Rev Mol Cell Biol. 2013 Nov;14(11):687. (PMID: 24129416)
Comment in: Dev Cell. 2013 Oct 28;27(2):126-7. (PMID: 24176638)
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معلومات مُعتمدة: R01 CA133228 United States CA NCI NIH HHS; R01 GM052022 United States GM NIGMS NIH HHS; TGM11CB3 Italy TI_ Telethon; CA133228 United States CA NCI NIH HHS
المشرفين على المادة: 0 (OFD1 protein, mouse)
0 (Proteins)
تواريخ الأحداث: Date Created: 20131004 Date Completed: 20131211 Latest Revision: 20220321
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4075283
DOI: 10.1038/nature12606
PMID: 24089205
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4687
DOI:10.1038/nature12606