The cilia protein IFT88 is required for spindle orientation in mitosis

Nature Cell Biology
Benedicte DelavalStephen Doxsey


Cilia dysfunction has long been associated with cyst formation and ciliopathies. More recently, misoriented cell division has been observed in cystic kidneys, but the molecular mechanism leading to this abnormality remains unclear. Proteins of the intraflagellar transport (IFT) machinery are linked to cystogenesis and are required for cilia formation in non-cycling cells. Several IFT proteins also localize to spindle poles in mitosis, indicating uncharacterized functions for these proteins in dividing cells. Here, we show that IFT88 depletion induces mitotic defects in human cultured cells, in kidney cells from the IFT88 mouse mutant Tg737(orpk) and in zebrafish embryos. In mitosis, IFT88 is part of a dynein1-driven complex that transports peripheral microtubule clusters containing microtubule-nucleating proteins to spindle poles to ensure proper formation of astral microtubule arrays and thus proper spindle orientation. This work identifies a mitotic mechanism for a cilia protein in the orientation of cell division and has important implications for the etiology of ciliopathies.


Aug 1, 1979·Journal of Ultrastructure Research·C L RiederL C Jensen
Sep 1, 1992·The Journal of Cell Biology·I Corthésy-TheulazS R Pfeffer
Jan 1, 1995·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·D N Wheatley
Feb 11, 1999·The Journal of Cell Biology·Gregory J PazourGeorge B Witman
Jun 10, 2000·Molecular Biology of the Cell·A YoungStephen Doxsey
Sep 25, 2001·Trends in Cell Biology·C L RiederA Khodjakov
Sep 6, 2002·The Journal of Cell Biology·Stephen L RogersRonald D Vale
Nov 5, 2002·Nature Reviews. Molecular Cell Biology·Joel Rosenbaum, George B Witman
Oct 3, 2003·Current Biology : CB·Young-Goo HanMaurice J Kernan
Mar 17, 2004·The Journal of Cell Biology·Carlo IominiGianni Piperno
Jul 21, 2005·Molecular Biology of the Cell·Rebecca A GreenKenneth B Kaplan
Dec 13, 2005·Nature Reviews. Genetics·Friedhelm Hildebrandt, Edgar Otto
Dec 13, 2005·Nature Genetics·Evelyne FischerMarco Pontoglio
Mar 11, 2006·Current Biology : CB·U Serdar TuluPatricia Wadsworth
Jan 25, 2007·Nature Reviews. Molecular Cell Biology·Jens Lüders, Tim Stearns
Jan 27, 2007·Science·Yukiko M YamashitaMargaret T Fuller
Mar 3, 2007·Nature Cell Biology·Keith MikuleStephen Doxsey
Jan 9, 2008·The Journal of Cell Biology·Jonathan M Scholey
Mar 3, 2009·Cell Motility and the Cytoskeleton·John A FollitGregory J Pazour
May 1, 1993·Roux's Archives of Developmental Biology : the Official Organ of the EDBO·Beate SchmitzJosé A Campos-Ortega


Jul 12, 2012·Cellular and Molecular Life Sciences : CMLS·Junmin PanErica A Golemis
Mar 12, 2013·Cellular and Molecular Life Sciences : CMLS·Hidemasa GotoMasaki Inagaki
Feb 4, 2012·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Andrew S ChuRebecca G Wells
Jun 3, 2011·Nature Cell Biology·Rieko Ajima, Hiroshi Hamada
Feb 7, 2012·Nature Neuroscience·Natsuko KumamotoShaoyu Ge
Nov 2, 2012·Molecular Biology of the Cell·Brian A BaylessChad G Pearson
Jan 29, 2013·Cilia·Helen L May-Simera, Matthew W Kelley
Dec 6, 2012·Biology Open·Ekaterina BubenshchikovaTomoko Obara
Jan 10, 2012·Development·Edwin C Oh, Nicholas Katsanis
Jan 28, 2012·Journal of the American Society of Nephrology : JASN·Julie A JonassenGregory J Pazour
Jun 21, 2013·Human Molecular Genetics·Monique N H LuijtenMaurice A M van Steensel
Mar 26, 2014·The Journal of Cell Biology·Yagmur TurgayUlrike Kutay
Jan 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·Yunfan YangJun Zhou
Dec 3, 2013·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Eugenia PapakrivopoulouDavid A Long
Nov 13, 2014·Médecine sciences : M/S·Christine Laclef
Oct 25, 2014·Nature Communications·Nicoletta I Petridou, Paris A Skourides
Dec 26, 2012·The Journal of Cell Biology·Anna NoatynskaPatrick Meraldi
Mar 20, 2013·The Journal of Cell Biology·Mei ZhuIngrid Hoffmann
Jul 27, 2011·The Journal of Cell Biology·Zita Carvalho-SantosMónica Bettencourt-Dias
Apr 9, 2013·Seminars in Cell & Developmental Biology·Jérôme Ezan, Mireille Montcouquiol
Dec 20, 2011·Differentiation; Research in Biological Diversity·Prachee Avasthi, Wallace F Marshall
Nov 29, 2011·Differentiation; Research in Biological Diversity·Michael TaschnerEsben Lorentzen
Dec 30, 2014·Cell Metabolism·Edwin C OhNicholas Katsanis
Mar 17, 2016·Cilia·Anastassiia VertiiStephen Doxsey
Dec 23, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Peter Satir
Dec 18, 2012·Nephrology·James A DeaneSharon D Ricardo
Jan 15, 2014·The EMBO Journal·Anaïs BouissouBrigitte Raynaud-Messina
Feb 11, 2015·Cell Cycle·Edmarcia Elisa de SouzaJörg Kobarg
Jan 8, 2015·Journal of Medical Genetics·Aoife M WatersPhilip L Beales
Apr 15, 2015·Nature Reviews. Nephrology·Tamina Seeger-NukpezahErica A Golemis
Aug 5, 2011·Cell Cycle·Sehyun Kim, Leonidas Tsiokas
Feb 25, 2014·Developmental Cell·Heidi Hehnly, Stephen Doxsey
Feb 28, 2015·Developmental Biology·Mi-Sun LeeCheol-Hee Kim
Aug 3, 2016·The Journal of Cell Biology·Carolyn M Ott

Methods Mentioned

gel filtration
antisense oligonucleotides
flow cytometry

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