The cilia protein IFT88 is required for spindle orientation in mitosis
Program in Molecular Medicine; Program in Gene Function and Expression
Anatomy; Animals; Cell Line; Cilia; Hela Cells; Humans; Kidney; Mice; Mice, Transgenic; Microtubules; *Mitosis; Mitotic Spindle Apparatus; Recombinant Fusion Proteins; Tubulin; Tumor Suppressor Proteins; Zebrafish; Zebrafish Proteins
Cell Biology | Cellular and Molecular Physiology | Molecular Genetics
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.
DOI of Published Version
Nat Cell Biol. 2011 Apr;13(4):461-8. Epub 2011 Mar 27. Link to article on publisher's site
Nature cell biology
Delaval, Benedicte; Bright, Alison; Lawson, Nathan D.; and Doxsey, Stephen J., "The cilia protein IFT88 is required for spindle orientation in mitosis" (2011). Program in Gene Function and Expression Publications and Presentations. 163.