CHD4 Is a RanGTP-Dependent MAP that Stabilizes Microtubules and Regulates Bipolar Spindle Formation

Yokoyama, Hideki; Nakos, Konstantinos; Santarella-Mellwig, Rachel; Rybina, Sofia; Krijgsveld, Jeroen; Koffa, Maria; Mattaj, Iain W.

doi:10.1016/j.cub.2013.09.062

Cited by 27 publications

(31 citation statements)

References 38 publications

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“…To test whether Mi-2 or NHK-1 are required for spindle formation, RNAi oocytes were immunostained for α-tubulin. A Mi-2 orthologue, CHD4, has been recently shown to bind microtubules and to be required for full spindle microtubule assembly and spindle bipolarity in Xenopus egg extract and cultured cells from humans and Drosophila ( Yokoyama et al, 2013 ). In Mi-2 RNAi oocytes, about a half of the oocytes had abnormal spindles ( supplementary material Fig.…”

Section: Resultsmentioning

confidence: 99%

The NuRD nucleosome remodelling complex and NHK-1 kinase are required for chromosome condensation in oocytes

Nikalayevich

Ohkura

2014

Journal of Cell Science

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Chromosome condensation during cell division is one of the most dramatic events in the cell cycle. Condensin and topoisomerase II are the most studied factors in chromosome condensation. However, their inactivation leads to only mild defects and little is known about the roles of other factors. Here, we took advantage of Drosophila oocytes to elucidate the roles of potential condensation factors by performing RNA interference (RNAi). Consistent with previous studies, depletion of condensin I subunits or topoisomerase II in oocytes only mildly affected chromosome condensation. In contrast, we found severe undercondensation of chromosomes after depletion of the Mi-2-containing NuRD nucleosome remodelling complex or the protein kinase NHK-1 (also known as Ballchen in Drosophila). The further phenotypic analysis suggests that Mi-2 and NHK-1 are involved in different pathways of chromosome condensation. We show that the main role of NHK-1 in chromosome condensation is to phosphorylate Barrier-to-autointegration factor (BAF) and suppress its activity in linking chromosomes to nuclear envelope proteins. We further show that NHK-1 is important for chromosome condensation during mitosis as well as in oocytes.

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Section: Resultsmentioning

confidence: 99%

The NuRD nucleosome remodelling complex and NHK-1 kinase are required for chromosome condensation in oocytes

Nikalayevich

Ohkura

2014

Journal of Cell Science

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“…It seems counterintuitive that overexpression of a mesh component results in skewed MTs; shouldn't it make the MTs in the fiber ‘more parallel’? However, it is likely that the mesh is made of other proteins, besides the TACC3–ch-TOG–clathrin complex, for example, CHD4, HURP/DLGAP5, and HSET/KIFC1 ( Mountain et al, 1999 ; Sharp et al, 1999 ; Koffa et al, 2006 ; Yokoyama et al, 2013 ). We favor the idea that because we have increased only one component of the mesh experimentally and not others, we do not see uniform changes in spacing and packing.…”

Section: Discussionmentioning

confidence: 99%

The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle

Nixon

Gutiérrez-Caballero

Hood

et al. 2015

eLife

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Kinetochore fibers (K-fibers) of the mitotic spindle are force-generating units that power chromosome movement during mitosis. K-fibers are composed of many microtubules that are held together throughout their length. Here, we show, using 3D electron microscopy, that K-fiber microtubules (MTs) are connected by a network of MT connectors. We term this network ‘the mesh’. The K-fiber mesh is made of linked multipolar connectors. Each connector has up to four struts, so that a single connector can link up to four MTs. Molecular manipulation of the mesh by overexpression of TACC3 causes disorganization of the K-fiber MTs. Optimal stabilization of K-fibers by the mesh is required for normal progression through mitosis. We propose that the mesh stabilizes K-fibers by pulling MTs together and thereby maintaining the integrity of the fiber. Our work thus identifies the K-fiber meshwork of linked multipolar connectors as a key integrator and determinant of K-fiber structure and function.DOI: http://dx.doi.org/10.7554/eLife.07635.001

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“…These include: (a) the tumor suppressor Adenomatous polyposis coli (Apc), which helps assemble and bundle microtubules [23], (b) two chromatin remodeling ATPases, CHD4 and ISWI, that act as Ran-dependent microtubule stabilizers [24,25], (c) a k-fiber stabilizer, MCRS1 [26], and (d) a set of nucleoporins (see below) [27,28]. Each of the above SAFs, both old and new, are hypothesized to be bound and inhibited by importin beta (or α/β) away from chromatin and released by RanGTP near chromatin.…”

Section: Spindle Assembly Factors: Extensive Regulationmentioning

confidence: 99%

Nuclear transport factors: global regulation of mitosis

Forbes

Travesa

Nord

et al. 2015

Current Opinion in Cell Biology

110

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The unexpected repurposing of nuclear transport proteins from their function in interphase to an equally vital and very different set of functions in mitosis was very surprising. The multi-talented cast when first revealed included the import receptors, importin alpha and beta, the small regulatory GTPase RanGTP, and a subset of nuclear pore proteins. In this review, we report that recent years have revealed new discoveries in each area of this expanding story in vertebrates: (a) The cast of nuclear transport receptors playing a role in mitotic spindle regulation has expanded: both transportin, a nuclear import receptor, and Crm1/Xpo1, an export receptor, are involved in different aspects of spindle assembly. Importin beta and transportin also regulate nuclear envelope and pore assembly. (b) The role of nucleoporins has grown to include recruiting the key microtubule nucleator the γ-TuRC complex and the exportin Crm1 to the mitotic kinetochores of humans. Together they nucleate microtubule formation from the kinetochores towards the centrosomes. (c) New research finds that the original importin beta/RanGTP team have been further co-opted by evolution to help regulate other cellular and organismal activities, ranging from the actual positioning of the spindle within the cell perimeter, to regulation of a newly discovered spindle microtubule branching activity, to regulation of the interaction of microtubule structures with specific actin structures. (d) Lastly, because of the multitudinous roles of karyopherins throughout the cell cycle, a recent large push toward testing their potential as chemotherapeutic targets has begun to yield burgeoning progress in the clinic.

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CHD4 Is a RanGTP-Dependent MAP that Stabilizes Microtubules and Regulates Bipolar Spindle Formation

Abstract: Our results uncover a new role for CHD4 as a MAP required for MT stabilization and involved in generating spindle bipolarity.

Cited by 27 publications

References 38 publications

The NuRD nucleosome remodelling complex and NHK-1 kinase are required for chromosome condensation in oocytes

The NuRD nucleosome remodelling complex and NHK-1 kinase are required for chromosome condensation in oocytes

The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle

Nuclear transport factors: global regulation of mitosis

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