The cilia protein IFT88 is required for spindle orientation in mitosis

Abstract

Cilia dysfunction has long been associated with cyst formation and ciliopathies1. More recently, misoriented cell division has been observed in cystic kidneys2, but the molecular mechanism leading to this abnormality remains unclear. Proteins of the intraflagellar transport (IFT) machinery are linked to cystogenesis and required for cilia formation in non-cycling cells3, 4. Several IFT proteins also localize to spindle poles in mitosis5–8 suggesting 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 Tg737orpk and in zebrafish embryos. In mitosis, IFT88 is part of a dynein1-driven complex that transports peripheral microtubule (MT) clusters containing MT-nucleating proteins to spindle poles to ensure proper formation of astral MT arrays and thus, proper spindle orientation. This work identifies a mitotic molecular mechanism for a cilia protein in the orientation of cell division and thus, has important implications for the etiology of ciliopathies.