IFT proteins spatially control the geometry of cleavage furrow ingression and lumen positioning

Taulet, Nicolas; Vitre, Benjamin; Anguille, Christelle; Douanier, Audrey; Rocancourt, Murielle; Täschner, Michael; Lorentzen, Esben; Échard, Arnaud; Delaval, Bénédicte

doi:10.1038/s41467-017-01479-3

Cited by 21 publications

(39 citation statements)

References 43 publications

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“…Whether IFTs only contribute to chromosome alignment by controlling spindle integrity or whether they could also act elsewhere, for example at the kinetochore, will require further investigations. Of note, IFTs also serve as cargo adaptors at later mitotic stages to control central spindle organization 20 .…”

Section: Discussionmentioning

confidence: 99%

“…By characterizing a novel cilia-independent function for an IFT at the minusends of k-fibers, this work complements recent evidences that introduce new perspectives on cellular processes involving IFT proteins beyond their role in cilia. These include, in addition to cell cycle 31 and cell division 19,20,32 , immune synapse polarization 17,18,33 , cell migration 34 and the regulation of cytoplasmic MT dynamics 16 or actin 35 . Future works will be required to address whether IFTs function in these non-ciliary roles only as cargo adaptors or also as motor regulators as shown for ciliary motors 15 .…”

Section: Discussionmentioning

confidence: 99%

“…HeLa cells expressing Flag-IFT27 and YFP-NuMA were synchronized in mitosis. Flag IP was used, as previously described 20 , to pull-down IFT proteins including IFT88, and revealed an interaction with YFP-NuMA in mitotic cells. These experiments showed that the IFT machinery, including IFT88 and IFT27 can interact with NuMA in mitotic cells and that IFT88 is required for NuMA enrichment at k-fibers minus-ends after ablation.…”

Section: Ift88 Interacts With Numa and Is Required For Its Minus-end mentioning

confidence: 99%

“…Targeted proteins were depleted with small-interfering RNAs (siRNAs) designed and ordered via Dharmacon (Lafayette, CO), as previously described 20 , and delivered to cells at a final concentration of 100 nM using Oligofectamine (Invitrogen, Carlsbad, CA) according to manufacturers' instructions. The efficacy of proteins knockdown was assessed by immunoblotting 48 h post transfection.…”

Section: Aid Cell Line Sirna and Cdna Transfectionsmentioning

confidence: 99%

“…Interestingly, in addition to their ciliary roles, IFTs were also shown to function in interphase in the regulation of MT dynamics in the cytoplasm 16 . Moreover, they were shown to contribute to intracellular transport in non-ciliary systems such as lymphocytes 17,18 or dividing cells 19,20 . Indeed, in mitosis, IFT88 was previously shown to function as part of a dynein1-driven complex required for the transport of peripheral MT clusters to spindle poles to ensure proper formation of astral MT arrays and correct spindle orientation 19 .…”

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confidence: 99%

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IFT88 controls NuMA enrichment at k-fibers minus-ends to facilitate their reincorporation into mitotic spindles

Taulet

Douanier

Vitre

et al. 2019

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To build and maintain mitotic spindle architecture, molecular motors exert spatially regulated forces on microtubules (MT) minus-ends. This spatial regulation is required to allow proper chromosomes alignment through the organization of kinetochore fibers (k-fibers). NuMA was recently shown to target dynactin to MT minus-ends and thus to spatially regulate dynein activity. However, given that k-fibers are embedded in the spindle, our understanding of the machinery involved in the targeting of proteins to their minus-ends remains limited. Intraflagellar transport (IFT) proteins were primarily studied for their ciliary roles but they also emerged as key regulators of cell division. Taking advantage of MT laser ablation, we show here that IFT88 concentrates at k-fibers minus-ends and is required for their re-anchoring into spindles by controlling NuMA accumulation. Indeed, IFT88 interacts with NuMA and is required for its enrichment at newly generated k-fibers minus-ends. Combining nocodazole washout experiments and IFT88 depletion, we further show that IFT88 is required for the reorganization of k-fibers into spindles and thus for efficient chromosomes alignment in mitosis. Overall, we propose that IFT88 could serve as a mitotic MT minus-end adaptor to concentrate NuMA at minus-ends thus facilitating kfibers incorporation into the main spindle.can be considered as a platform for such a regulation. Indeed, NuMA was recently shown to target dynactin to minus-ends and thus spatially regulate dynein activity 8,9 . If proteins recruitment at MT plus-end has been well-documented, the specific targeting of proteins to MTs and k-fiber minusends has yet to be fully understood 10 . Indeed, continuous reintegration of k-fibers happens inside an established spindle and is essential to preserve its integrity and to ensure proper chromosomes alignment 6-8 . However, given that k-fibers are embedded in the main spindle, our understanding of the machinery involved in the targeting of proteins to their minus-ends remains limited.The intraflagellar transport (IFT) machinery is a well conserved intra-cellular transport system that has been studied for a long time for its role in cilia formation and function in non-dividing cells 11 .During IFT-mediated transport, kinesin and dynein motors drive the bidirectional transport of IFT trains from the base to the tip of the cilium in an anterograde movement and from the tip to the base in a retrograde movement 12 . IFTs were therefore accepted to function as cargos, for example, of axoneme precursors such as tubulins as well as molecules of the signal transduction machinery inside the cilium 13,14 . More recently, IFTs were shown to contribute to ciliary motor activation 15 indicating that a lot remains to be done to fully understand the roles of this complex machinery. Interestingly, in addition to their ciliary roles, IFTs were also shown to function in interphase in the regulation of MT dynamics in the cytoplasm 16 . Moreover, they were shown to contribute to intracellular transport in n...

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Section: Discussionmentioning

confidence: 99%