Kif2a depletion generates chromosome segregation and pole coalescence defects in animal caps and inhibits gastrulation of the<i>Xenopus</i>embryo

Eagleson, Gerald W.; Pfister, Katherine; Knowlton, Ann L.; Skoglund, Paul; Keller, Ray; Stukenberg, P. Todd

doi:10.1091/mbc.e13-12-0721

Cited by 15 publications

(23 citation statements)

References 41 publications

(77 reference statements)

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“…At the M II stage, Kif2a was again localized at the spindle poles and the spindle microtubules, and also around the centromeres. This localization pattern for Kif2a is slightly different from that reported for Kif2a in mitosis1117.…”

Section: Resultscontrasting

confidence: 97%

“…Kif2a is identified as a kinesin-13 microtubule depolymerase that regulates spindle organization, and chromosome movement in mitosis1727. However, its requirements for oocyte meiotic maturation is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Kif2a is localized to spindle microtubules, concentrates at spindle poles in Hela cells11 and at kinetochores in Xenopus cells17. Kif2a is found abundantly expressed in neurons, in which Kif2a depolymerizes MTs to suppress the growth of axonal collateral branches1819.…”

mentioning

confidence: 99%

“…Kif2a is also required for spindle assembly in mitosis where it is thought to depolymerize microtubules at the minus ends at the poles, thereby maintaining spindle length621. Depletion of Kif2a generates monopolar spindles in Hela cells11, while it contributes to multipolar spindles and failure of pole coalescence in Xenopus embryos17. The pesticide dichlorvos induced spindle monopolarity by inhibiting the depolymerizing activity of Kif2a at centrosomes22.…”

mentioning

confidence: 99%

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Kif2a regulates spindle organization and cell cycle progression in meiotic oocytes

Liang

et al. 2016

Sci Rep

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Kif2a is a member of the Kinesin-13 microtubule depolymerases. Here, we report the expression, subcellular localization and functions of Kif2a during mouse oocyte meiotic maturation. Immunoblotting analysis showed that Kif2a was gradually increased form GV to the M I stages, and then decreased slightly at the M II stage. Confocal microscopy identified that Kif2a localized to the meiotic spindle, especially concentrated at the spindle poles and inner centromeres in metaphase and translocated to the midbody at telophase. Kif2a depletion by siRNA microinjection generated severely defective spindles and misaligned chromosomes, reduced microtubule depolymerization, which led to significant pro-M I/M Iarrest and failure of first polar body (PB1) extrusion. Kif2a-depleted oocytes were also defective in spindle pole localization of γ-tubulin and showed spindle assembly checkpoint (SAC) protein Bub3 at the kinetochores even after 10 hr extended culture. These results demonstrate that Kif2a may act as a microtubule depolymerase, regulating microtubule dynamics, spindle assembly and chromosome congression, and thus cell cycle progression during mouse oocyte meiotic maturation.

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Section: Resultscontrasting

confidence: 97%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Kif2a regulates spindle organization and cell cycle progression in meiotic oocytes

Liang

et al. 2016

Sci Rep

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“…65 In mitotic cells, Kif2A has been implicated in mitotic spindle size scaling and centrosome coalescence. 66,67 In interphase cells, Kif2A has been found to affect microtubule dynamics 68 and collateral axonal branch extension. 64 Kif2 has been reported to affect lysosomal positioning 69 and primary cilium disassembly in preparation for cell figure) binding to the PH domain of ASAP1 facilitates ArfGTP binding to ASAP1.…”

Section: Agap1 and Kif2amentioning

confidence: 99%

Arf GAPs and molecular motors

et al. 2017

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Arf GTPase-activating proteins (Arf GAPs) were first identified as regulators of the small GTP-binding proteins ADP-ribosylation factors (Arfs). The Arf GAPs are a large family of proteins in metazoans, outnumbering the Arfs that they regulate. The members of the Arf GAP family have complex domain structures and some have been implicated in particular cellular functions, such as cell migration, or with particular pathologies, such as tumor invasion and metastasis. The specific effects of Arfs sometimes depend on the Arf GAP involved in their regulation. These observations have led to speculation that the Arf GAPs themselves may affect cellular activities in capacities beyond the regulation of Arfs. Recently, 2 Arf GAPs, ASAP1 and AGAP1, have been found to bind directly to and influence the activity of myosins and kinesins, motor proteins associated with filamentous actin and microtubules, respectively. The Arf GAP-motor protein interaction is critical for cellular behaviors involving the actin cytoskeleton and microtubules, such as cell migration and other cell movements. Arfs, then, may function with molecular motors through Arf GAPs to regulate microtubule and actin remodeling.

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Wnt signaling recruits KIF2A to the spindle to ensure chromosome congression and alignment during mitosis

Bufe

Arco

Hennecke

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Significance Wnt signaling plays essential roles in embryonic patterning, stem cell renewal, and cell cycle progression from G1 to S phase via the regulation of β-catenin target genes. Here, we show that Wnt signaling also promotes timely execution of mitosis. We demonstrate that the Wnt signaling transducer Dishevelled recruits the mitotic kinesin KIF2A and mediates its binding to the mitotic spindle. KIF2A is a microtubule depolymerase that controls chromosome alignment and congression during mitosis. Consequently, we found that inhibition of Wnt signaling leads to KIF2A-dependent chromosome congression and alignment delay in somatic and pluripotent stem cells.

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Kif2a depletion generates chromosome segregation and pole coalescence defects in animal caps and inhibits gastrulation of theXenopusembryo

Abstract: Characterization of Kif2a in Xenopus embryos identifies new roles for the Kif2a microtubule depolymerase in coordinating cytokinesis and centrosome coalescence. In addition, defects in mitosis can inhibit large-scale developmental movements in vertebrate tissues.

Cited by 15 publications

References 41 publications

Kif2a regulates spindle organization and cell cycle progression in meiotic oocytes

Kif2a regulates spindle organization and cell cycle progression in meiotic oocytes

Arf GAPs and molecular motors

Wnt signaling recruits KIF2A to the spindle to ensure chromosome congression and alignment during mitosis

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