Where “IntraFlagellar Transport” meets “IntraMitotic Transport” : Novel roles for cilia proteins in cell division

Orateur : Bénédicte DELAVAL (CRBM, CNRS, Montpellier)

An emerging group of human genetic diseases termed ’ciliopathies’ are caused by the dysfunction of two functionally and physically associated organelles, the centrosome and the cilium. These pathologies display multi-organ involvement including brain, kidney or retina. However, the cellular mechanisms underlying many of the ciliopathy-related phenotypes have yet to be fully elucidated. Disruption of cilia proteins, such as proteins of the intraflagellar transport (IFT) machinery, has been associated with polycystic kidney disease. Given the role of these proteins in cilia formation, ciliopathy-related phenotypes have long been thought to stem exclusively from absence or dysfunctions of cilia. Interestingly, several core cilia proteins localize to spindle poles in mitosis suggesting uncharacterized functions for these proteins in dividing cells. We recently showed that the cilia protein IFT88 functions in mitosis to ensure correct spindle orientation. Indeed, IFT88 depletion induces mitotic defects in human cultured cells, 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 clusters to spindle poles to ensure proper formation of astral microtubule arrays and thus, proper spindle orientation. Using an original and powerful approach that combines cell biology and mass-spectrometry based approaches in cultured cells with the use of zebrafish (Danio rerio) as an in vivo platform to study cellular processes associated with tissue morphogenesis, we are currently investigating the role of cilia proteins of the IFT machinery in non-ciliated dividing cells. In light of these findings, we might reconsider a purely cilium-based hypothesis, and instead propose that a subset of ciliopathy-related phenotypes may arise from a combination of cilium-mediated and non-ciliary roles of cilia proteins.

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