Ran
            <scp>GTP</scp>
            and importin β regulate meiosis I spindle assembly and function in mouse oocytes

Drutovič, Dávid; Duan, Xing; Li, Rong; Kaláb, Petr; Solc, P

doi:10.15252/embj.2019101689

Cited by 42 publications

(37 citation statements)

References 71 publications

(139 reference statements)

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“…Additional SAFs include, among others, Anillin, APC, MCRS1, and the kinesins Kif2a and Kif14 (reviewed in [131]). The Ran pathway is particularly important in oocytes, which are-under physiological conditions-the only dividing cell type that degrades centrosomes [139][140][141]. While dividing mouse oocytes assemble numerous acentrosomal MTOCs containing PCNT, γ-tubulin, NEDD1, and CEP192 [142], a prominent acentrosomal MTOC in human oocytes remains elusive [143,144].…”

Section: Centrosome-independent Microtubule Organizing Pathwaysmentioning

confidence: 99%

Microtubule Organization in Striated Muscle Cells

Becker

Leone

Engel

2020

Cells

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Distinctly organized microtubule networks contribute to the function of differentiated cell types such as neurons, epithelial cells, skeletal myotubes, and cardiomyocytes. In striated (i.e., skeletal and cardiac) muscle cells, the nuclear envelope acts as the dominant microtubule-organizing center (MTOC) and the function of the centrosome—the canonical MTOC of mammalian cells—is attenuated, a common feature of differentiated cell types. We summarize the mechanisms known to underlie MTOC formation at the nuclear envelope, discuss the significance of the nuclear envelope MTOC for muscle function and cell cycle progression, and outline potential mechanisms of centrosome attenuation.

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Section: Centrosome-independent Microtubule Organizing Pathwaysmentioning

confidence: 99%

Microtubule Organization in Striated Muscle Cells

Becker

Leone

Engel

2020

Cells

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“…We then asked whether Ran-GDP accumulated in specific subcellular locations in cyst cells. We over-expressed an HA-tagged Ran T24N , which carries an amino acid substitution that locks Ran into a GDP-bound state and inhibits cargo loading (Cesario and McKim, 2011; Drutovic et al, 2020). As expected, Ran-GDP was primarily cytoplasmic in interphase cells (Figure 3C).…”

Section: Resultsmentioning

confidence: 99%

β-importins Tnpo-SR and Cadmus and the small GTPase Ran promote ovarian cyst formation inDrosophila

Williams

et al. 2021

Preprint

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Germ cells undergo mitotic expansion via incomplete cytokinesis, forming cysts of undifferentiated cells that remain interconnected prior to meiotic initiation, through mechanisms that are not well-defined. In somatic cells, an actomyosin contractile network controls cleavage furrow formation and abscission and is spatiotemporally regulated by Ras-related nuclear protein (Ran). Here, we identify Ran and β-importins as critical regulators of cyst development in the Drosophila ovary. Depletion of Ran or the β-importins Tnpo-SR and cadmus disrupts oocyte selection and results in egg chambers with variable numbers of germ cells, suggesting abnormal cyst development and cyst fragmentation. We demonstrate that Ran, Tnpo-SR, and Cadmus regulate key cellular processes during cyst formation, including cell cycle dynamics, fusome biogenesis, and ring canal stability, yet do so independently of mitotic spindle assembly. Further, Tnpo-SR and Cadmus control cyclin accumulation and suppress cytokinesis independent of Ran-GTP, suggesting that β-importins sequester protein cargos that normally promote the mitotic-to-meiotic transition. Our data demonstrates that Ran and β-importins are critical for germ cell cyst formation, a role that is likely conserved in other organisms.

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“…Using the same strategy, we next examined the effects of Cdc42 inhibition in activated oocytes. We did not consider inhibiting the upstream Ran GTPase, as RanGTP plays an additional role in maintaining spindle integrity (19,49). Thus, we recorded confocal time-series of parthenogenetically activated oocytes expressing Cdc42T17N and H2b-mCherry, and we observed two distinct phenotypes ( Fig 5D and S9 Movie).…”

Section: The Polarized Cortex Exerts Attraction Forces On Chromatidsmentioning

confidence: 99%

RhoA- and Ran-induced antagonistic forces underlie symmetry breaking and spindle rotation in mouse oocytes

Dehapiot

Clément

Bourdais

et al. 2020

Preprint

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Mammalian oocyte meiotic divisions are highly asymmetric and produce a large haploid gamete and two small polar bodies. This relies on the ability of the cell to break symmetry and position its spindle close to the cortex before the anaphase occurs. In metaphase II arrested mouse oocytes, the spindle is actively maintained close and parallel to the cortex, until the fertilization triggers the sister chromatids segregation and the rotation of the spindle. The latter must indeed reorient perpendicular to the cortex to enable the cytokinesis ring closure at the base of the polar body. However, the mechanisms underlying symmetry breaking and spindle rotation have remained elusive. In this study, we show that the spindle rotation results from two antagonistic forces. First, an inward contraction of the cytokinesis furrow dependent on RhoA signaling and second, an outward attraction exerted on both lots of chromatids by a RanGTP dependent polarization of the actomyosin cortex. By combining live segmentation and tracking with numerical modelling, we demonstrate that this configuration becomes unstable as the ingression progresses. This leads to spontaneous symmetry breaking, which implies that neither the rotation direction nor the lot of chromatids that eventually gets discarded are biologically predetermined.

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Ran GTP and importin β regulate meiosis I spindle assembly and function in mouse oocytes

Cited by 42 publications

References 71 publications

Microtubule Organization in Striated Muscle Cells

Microtubule Organization in Striated Muscle Cells

β-importins Tnpo-SR and Cadmus and the small GTPase Ran promote ovarian cyst formation inDrosophila

RhoA- and Ran-induced antagonistic forces underlie symmetry breaking and spindle rotation in mouse oocytes

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