title: The cilia protein IFT88 is required for spindle orientation in mitosis.
abstract: 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.
authors: Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Suite 210, Worcester, Massachusetts 01605, USA.
authors: Benedicte
authors: B
authors: Delaval
authors: Alison
authors: A
authors: Bright
authors: Nathan D
authors: ND
authors: Lawson
authors: Stephen
authors: S
authors: Doxsey
mesh_terms: D000715:Anatomy; D000818:Animals; D002460:Cell Line; D002923:Cilia / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C098623:IFT88 protein, human; D011993:Recombinant Fusion Proteins; C490898:Tg737Rpw protein, mouse; D014404:Tubulin; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins