Ran GTPase promotes oocyte polarization by regulating ERM (Ezrin/Radixin/Moesin) inactivation

Dehapiot, Benoît; Halet, Guillaume

doi:10.4161/cc.24901

Cited by 36 publications

(47 citation statements)

References 48 publications

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“…76 The RAN GTP gradient is also involved in the polarization of the inactive Ezrin-Radixin-Moesin (ERM) protein in oocytes. 77 However, the signaling pathway connecting RAN with ARP2/3-mediated actin polymerization is poorly understood. In addition to the small GTPase pathway, the actin polymerization pathway may be connected with well-known signaling pathways governing the cell cycle, including the MPF or Mos-MAP kinase pathways, and elucidation of these mechanisms could be critical for increasing our understanding of the regulation of ARP2/3-mediated actin polymerization based on cell cycle progression.…”

Section: The Arp2/3 Complex and Nucleation-promoting Factormentioning

confidence: 99%

“…84 p-ERM is localized near the cortex but is excluded from the region near the spindle. 77,123 The RAN GTP signal is associated with exclusion of p-ERM near the spindle. 77 oocyte maturation.…”

Section: Introductionmentioning

confidence: 99%

“…77,123 The RAN GTP signal is associated with exclusion of p-ERM near the spindle. 77 oocyte maturation. The novel small molecule inhibitor SMIFH2, 49 which binds to and inhibits the actin nucleation activity of the FH2 domain, inhibits several formin proteins in cells and has been used to treat immature oocytes, blocking various stages of oocyte maturation and resulting in phenotypes distinct from those of Fmn2(¡/¡) knockout oocytes.…”

Section: Introductionmentioning

confidence: 99%

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Roles of actin binding proteins in mammalian oocyte maturation and beyond

Namgoong

Kim

2016

Cell Cycle

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Actin nucleation factors, which promote the formation of new actin filaments, have emerged in the last decade as key regulatory factors controlling asymmetric division in mammalian oocytes. Actin nucleators such as formin-2, spire, and the ARP2/3 complex have been found to be important regulators of actin remodeling during oocyte maturation. Another class of actin-binding proteins including cofilin, tropomyosin, myosin motors, capping proteins, tropomodulin, and Ezrin-Radixin-Moesin proteins are thought to control actin cytoskeleton dynamics at various steps of oocyte maturation. In addition, actin dynamics controlling asymmetric-symmetric transitions after fertilization is a new area of investigation. Taken together, defining the mechanisms by which actin-binding proteins regulate actin cytoskeletons is crucial for understanding the basic biology of mammalian gamete formation and pre-implantation development.

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Section: The Arp2/3 Complex and Nucleation-promoting Factormentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Roles of actin binding proteins in mammalian oocyte maturation and beyond

Namgoong

Kim

2016

Cell Cycle

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“…http://dx.doi.org/10.1101/180869 doi: bioRxiv preprint first posted online Aug. 25, 2017; 3 The cortex overlying the spindle is polarized by the chromosomes, through a chromatin-based gradient of RAN GTP (21,22) (Fig. 2A).…”

mentioning

confidence: 99%

“…The cortex overlying the spindle is polarized by the chromosomes, through a chromatin-based gradient of RAN GTP (21,22) (Fig. 2A).…”

mentioning

confidence: 99%

Spindle asymmetry drives non-Mendelian chromosome segregation

Akera

Chmátal

Trimm

et al. 2017

Preprint

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Genetic elements compete for transmission through meiosis, when haploid gametes are created from a diploid parent. Selfish elements can enhance their transmission through meiotic drive, in violation of Mendel's Law of Segregation. In female meiosis, selfish elements drive by preferentially attaching to the egg side of the spindle, which implies some asymmetry between the two sides of the spindle, but molecular mechanisms underlying spindle asymmetry are unknown. Here we show that CDC42 signaling from the cell cortex regulates microtubule tyrosination to induce spindle asymmetry, and non-Mendelian segregation depends on this asymmetry. These signals depend on cortical polarization directed by chromosomes, which are positioned near the cortex to allow the asymmetric cell division. Thus, selfish meiotic drivers exploit the asymmetry inherent in female meiosis to bias their transmission.Genetic conflict is inherent in any haploid-diploid life cycle because genetic elements compete for transmission to the offspring through meiosis, the process by which haploids are generated. Mendel's Law of Segregation states that alleles of a gene are transmitted with equal probability, but it is increasingly clear that this law is often violated, and segregation can be manipulated by selfish genetic elements through meiotic drive. Drive can occur by eliminating competing gametes that do not contain the selfish element (e.g., sperm killing or spore killing) or by exploiting the asymmetry in female meiosis to increase the transmission of the selfish element to the egg. Although the impact of meiotic drive on many aspects of evolution and genetics is now recognized, with examples widespread across eukaryotes (1-4), the underlying mechanisms are largely unknown.Female meiosis provides a clear opportunity for selfish elements to cheat because of its inherent asymmetry: only chromosomes that segregate to the egg can be transmitted to offspring, while the rest are degraded in polar bodies. Conceptually, female meiotic drive depends on three conditions: asymmetry in cell fate, a functional not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/180869 doi: bioRxiv preprint first posted online Aug. 25, 2017; 2 difference between homologous chromosomes that influences their segregation, and asymmetry within the meiotic spindle (5). The asymmetry in cell fate is well established (6), and chromosomal rearrangements and amplifications of repetitive sequences (e.g., centromeres) are associated with biased segregation (7-10). Asymmetry within the meiotic spindle was noted in grasshopper in 1976 (11), but not studied further, and molecular mechanisms regulating such asymmetry are unknown.Oocyte spindles are positioned close to the cortex and oriented perpendicular to the cortex in order to achieve the highly asymmetric cell division, so that cytokinesis produces a large egg and a small polar body (Fig. 1A). A selfish element ...

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X centromeric drive may explain the prevalence of polycystic ovary syndrome and other conditions

Moore

2024

BioEssays

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X chromosome centromeric drive may explain the prevalence of polycystic ovary syndrome and contribute to oocyte aneuploidy, menopause, and other conditions. The mammalian X chromosome may be vulnerable to meiotic drive because of X inactivation in the female germline. The human X pericentromeric region contains genes potentially involved in meiotic mechanisms, including multiple SPIN1 and ZXDC paralogs. This is consistent with a multigenic drive system comprising differential modification of the active and inactive X chromosome centromeres in female primordial germ cells and preferential segregation of the previously inactivated X chromosome centromere to the polar body at meiosis I. The drive mechanism may explain differences in X chromosome regulation in the female germlines of the human and mouse and, based on the functions encoded by the genes in the region, the transmission of X pericentromeric genetic or epigenetic variants to progeny could contribute to preeclampsia, autism, and differences in sexual differentiation.

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Ran GTPase promotes oocyte polarization by regulating ERM (Ezrin/Radixin/Moesin) inactivation

Cited by 36 publications

References 48 publications

Roles of actin binding proteins in mammalian oocyte maturation and beyond

Roles of actin binding proteins in mammalian oocyte maturation and beyond

Spindle asymmetry drives non-Mendelian chromosome segregation

X centromeric drive may explain the prevalence of polycystic ovary syndrome and other conditions

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