FORMIN a link between kinetochores and microtubule ends

Mao, Yinghui

doi:10.1016/j.tcb.2011.08.005

Cited by 30 publications

(24 citation statements)

References 54 publications

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“…Diaphanous-related formins (Dia) are a subgroup of formins and there are three Dia proteins in mammals: Dia1, Dia2 and Dia3 (Campellone and Welch., 2010). Dia proteins are required for proper spindle formation, actin tubulin organization, cytokinesis and microtubule-kinetochore attachment (Ishizaki et al, 2001;Watanabe et al, 2008;Bartolini et al, 2008;Cheng et al, 2011;Mao, 2011). The budding yeast Diaphanous-related formins, Bni1 and Bnr1, are important for unequal cell division (Sagot et al, 2002;Gao et al, 2010); however, roles of Dia proteins in PBE have not been studied.…”

Section: Introductionmentioning

confidence: 99%

The Mos-MAPK pathway regulates Diaphanous-related formin activity to drive cleavage furrow closure during polar body emission in starfish oocytes

Ucar

Tachibana

Kishimoto

2013

Journal of Cell Science

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SummaryMaintenance of spindle attachment to the cortex and formation of the cleavage furrow around the protruded spindle are essential for polar body extrusion (PBE) during meiotic maturation of oocytes. Although spindle movement to the cortex has been well-studied, how the spindle is maintained at the cortex during PBE is unknown. Here, we show that activation of Diaphanous-related formin mediated by mitogen-activated protein kinase (MAPK) is required for tight spindle attachment to the cortex and cleavage furrow closure during PBE in starfish (Asterina pectinifera) oocytes. A. pectinifera Diaphanous-related formin (ApDia) had a distinct localization in immature oocytes and was localized to the cleavage furrow during PBE. Inhibition of the Mos-MAPK pathway or the actin nucleating activity of formin homology 2 domain prevented cleavage furrow closure and resulted in PBE failure. In MEK/MAPK-inhibited oocytes, activation of ApDia by relief of its intramolecular inhibition restored PBE. In summary, this study elucidates a link between the Mos-MAPK pathway and Diaphanous-related formins, that is responsible for maintaining tight spindle attachment to the cortex and cleavage furrow closure during PBE.

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Section: Introductionmentioning

confidence: 99%

The Mos-MAPK pathway regulates Diaphanous-related formin activity to drive cleavage furrow closure during polar body emission in starfish oocytes

Ucar

Tachibana

Kishimoto

2013

Journal of Cell Science

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“…Diaphanous formins are well known for their functions in polymerizing linear actin filaments and stabilizing microtubules. [33][34][35] The microtubule stabilization activity seems unlikely to be involved in mDia2's CENP-A function, as tubulins and microtubules are not normally found inside the nucleus. 36 On the contrary, recent works from multiple groups have implicated functional roles for the actin nucleation activity of formin proteins inside the nucleus.…”

Section: A Rho Family Small Gtpase Molecular Switch Is Required For Nmentioning

confidence: 99%

Formin-mediated epigenetic maintenance of centromere identity

Liu

Mao

2016

Small GTPases

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Accurate chromosome segregation in mammalian cells is guided by the centromere, a specialized chromosome region defined by the histone H3 variant centromere protein A (CENP-A). It is not well understood how cells maintain CENP-A levels at centromeres while continuously going through genome replications and cell divisions. A MgcRacGAP-dependent small GTPase molecular switch has been shown as essential for centromeric CENP-A maintenance. By using quantitative imaging, pulse-chase and live cell analysis, a recent work has suggested that the diaphanous formin mDia2, a well-established small GTPase effector, functions downstream of this small GTPase pathway to maintain CENP-A levels at centromeres. A constitutively active mDia2 construct is able to rescue the CENP-A loading defect caused by MgcRacGAP depletion. This study has uncovered an unsuspected role of the cytoskeleton protein mDia2 as an effector of the MgcRacGAP-dependent small GTPase signaling inside the nucleus to participate in the epigenetic regulation of centromere maintenance during cell cycle.

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“…While the actin cytoskeleton is required to position the meiotic spindle in some systems (Brunet and Verlhac 2011;Fabritius et al 2011;McNally 2013), it could also affect functioning of the spindle itself. Indeed, the formin mDIA3 has been shown to be involved in recruiting Aurora B for error correction (Mao 2011). RhoA has been shown to regulate microtubule stability, possibly through its downstream effectors mDia or Tau (Cook et al 1998;Waterman-Storer et al 2000;Palazzo et al 2001).…”

Section: A Hierarchy Of Central Spindle Assembly and Functionmentioning

confidence: 99%

Spindle Assembly and Chromosome Segregation Requires Central Spindle Proteins inDrosophilaOocytes

et al. 2015

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Oocytes segregate chromosomes in the absence of centrosomes. In this situation, the chromosomes direct spindle assembly. It is still unclear in this system which factors are required for homologous chromosome bi-orientation and spindle assembly. The Drosophila kinesin-6 protein Subito, although nonessential for mitotic spindle assembly, is required to organize a bipolar meiotic spindle and chromosome bi-orientation in oocytes. Along with the chromosomal passenger complex (CPC), Subito is an important part of the metaphase I central spindle. In this study we have conducted genetic screens to identify genes that interact with subito or the CPC component Incenp. In addition, the meiotic mutant phenotype for some of the genes identified in these screens were characterized. We show, in part through the use of a heat-shock-inducible system, that the Centralspindlin component RacGAP50C and downstream regulators of cytokinesis Rho1, Sticky, and RhoGEF2 are required for homologous chromosome bi-orientation in metaphase I oocytes. This suggests a novel function for proteins normally involved in mitotic cell division in the regulation of microtubulechromosome interactions. We also show that the kinetochore protein, Polo kinase, is required for maintaining chromosome alignment and spindle organization in metaphase I oocytes. In combination our results support a model where the meiotic central spindle and associated proteins are essential for acentrosomal chromosome segregation. KEYWORDS meiosis; synthetic lethal mutation; homolog bi-orientation; spindle; chromosome segregation; Drosophila C HROMOSOMES are segregated during cell division by the spindle, a bipolar array of microtubules. In somatic cells, spindle assembly is guided by the presence of centrosomes at the poles. In this conventional spindle assembly model, the kinetochores attach to microtubules from opposing centrosomes and tension is established. This satisfies the spindle assembly checkpoint, which then allows the cell to proceed to anaphase (Musacchio and Salmon 2007). Cell division is completed by recruiting proteins to a midzone of antiparallel microtubules that forms between the segregated chromosomes, signaling furrow formation (Fededa and Gerlich 2012;D'Avino et al. 2015). However, spindle morphogenesis in oocytes of many animals occurs in the absence of centrosomes. This may contribute to the high rates of segregation errors that are maternal in origin and are a leading cause of miscarriages, birth defects, and infertility (Herbert et al. 2015). How a robust spindle assembles without guidance from the centrosomes is not well understood. While it is clear that the chromosomes can recruit microtubules and drive spindle assembly (Tseng et al. 2010;Dumont and Desai 2012), how a bipolar spindle is organized and chromosomes make the correct attachments to microtubules is not understood.The Drosophila oocyte provides a genetically tractable system for the identification of genes involved in acentrosomal spindle assembly. Substantial evidence in Drosop...

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FORMIN a link between kinetochores and microtubule ends

Cited by 30 publications

References 54 publications

The Mos-MAPK pathway regulates Diaphanous-related formin activity to drive cleavage furrow closure during polar body emission in starfish oocytes

The Mos-MAPK pathway regulates Diaphanous-related formin activity to drive cleavage furrow closure during polar body emission in starfish oocytes

Formin-mediated epigenetic maintenance of centromere identity

Spindle Assembly and Chromosome Segregation Requires Central Spindle Proteins inDrosophilaOocytes

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