scholarly journals Cyclin B3 promotes APC/C activation and anaphase I onset in oocyte meiosis

2018 ◽  
Author(s):  
Mehmet E. Karasu ◽  
Nora Bouftas ◽  
Scott Keeney ◽  
Katja Wassmann
Keyword(s):  
Chromosome Segregation ◽  
Mammalian Cells ◽  
Cyclin B1 ◽  
Biochemical Properties ◽  
Cellular Functions ◽  
Meiotic Progression ◽  
Oocyte Meiosis ◽  
Sterile Mutant ◽  
Essential Function ◽  
Cyclin B3

As obligate kinase partners, cyclins control the switch-like cell cycle transitions that orchestrate orderly duplication and segregation of genomes. Meiosis, the cell division that generates gametes for sexual reproduction, poses unique challenges because two rounds of chromosome segregation must be executed without intervening DNA replication. Mammalian cells express numerous, temporally regulated cyclins, but how these proteins collaborate to control meiosis remains poorly understood. Here, we delineate an essential function for mouse cyclin B3 in the first meiotic division of oocytes. Females genetically ablated for cyclin B3 are viable, indicating the protein is dispensable for mitotic divisions, but are sterile. Mutant oocytes appear normal until metaphase I but then display a highly penetrant failure to transition to anaphase I. They arrest with hallmarks of defective APC/C activation, including no separase activity and high MPF, cyclin B1, and securin levels. Partial APC/C activation occurs, however, as exogenously expressed APC/C substrates can be degraded and arrest can be suppressed by inhibiting MPF kinase. Cyclin B3 is itself targeted for degradation by the APC/C. Cyclin B3 forms active kinase complexes with CDK1, and meiotic progression requires cyclin B3-associated kinase activity. Collectively, our findings indicate that cyclin B3 is essential for oocyte meiosis because it fine-tunes APC/C activity as a kinase-activating CDK partner. Cyclin B3 homologs from frog, zebrafish, and fruitfly rescue meiotic progression in cyclin B3-deficient mouse oocytes, indicating conservation of the biochemical properties and possibly cellular functions of this germline-critical cyclin.

scholarly journals Cyclin B3 promotes anaphase I onset in oocyte meiosis

2019 ◽  
Vol 218 (4) ◽  
pp. 1265-1281 ◽  
Author(s):  
Mehmet E. Karasu ◽  
Nora Bouftas ◽  
Scott Keeney ◽  
Katja Wassmann
Keyword(s):  
Mammalian Cells ◽  
Fruit Fly ◽  
Cyclin B1 ◽  
Biochemical Properties ◽  
Anaphase Promoting Complex ◽  
Cellular Functions ◽  
Meiotic Progression ◽  
Oocyte Meiosis ◽  
Sterile Mutant ◽  
Cyclin B3

Meiosis poses unique challenges because two rounds of chromosome segregation must be executed without intervening DNA replication. Mammalian cells express numerous temporally regulated cyclins, but how these proteins collaborate to control meiosis remains poorly understood. Here, we show that female mice genetically ablated for cyclin B3 are viable—indicating that the protein is dispensable for mitotic divisions—but are sterile. Mutant oocytes appear normal until metaphase I but then display a highly penetrant failure to transition to anaphase I. They arrest with hallmarks of defective anaphase-promoting complex/cyclosome (APC/C) activation, including no separase activity, high CDK1 activity, and high cyclin B1 and securin levels. Partial APC/C activation occurs, however, as exogenously expressed APC/C substrates can be degraded. Cyclin B3 forms active kinase complexes with CDK1, and meiotic progression requires cyclin B3–associated kinase activity. Cyclin B3 homologues from frog, zebrafish, and fruit fly rescue meiotic progression in cyclin B3–deficient mouse oocytes, indicating conservation of the biochemical properties and possibly cellular functions of this germline-critical cyclin.

scholarly journals The Cyclin B2/CDK1 Complex Conservatively Inhibits Separase Activity in Oocyte Meiosis II

2021 ◽  
Vol 9 ◽  
Author(s):  
Jian Li ◽  
Hong-Yong Zhang ◽  
Feng Wang ◽  
Qing-Yuan Sun ◽  
Wei-Ping Qian
Keyword(s):  
Chromosome Segregation ◽  
Homologous Chromosome ◽  
Cyclin B1 ◽  
Mouse Oocyte ◽  
Parthenogenetic Activation ◽  
Sister Chromatids ◽  
Oocyte Meiosis ◽  
Meiosis I

Recently, we have reported that the cyclin B2/CDK1 complex regulates homologous chromosome segregation through inhibiting separase activity in oocyte meiosis I, which further elucidates the compensation of cyclin B2 on cyclin B1’s function in meiosis I. However, whether cyclin B2/CDK1 complex also negatively regulates separase activity during oocyte meiosis II remains unknown. In the present study, we investigated the function of cyclin B2 in meiosis II of oocyte. We found that stable cyclin B2 expression impeded segregation of sister chromatids after oocyte parthenogenetic activation. Consistently, stable cyclin B2 inhibited separase activation, while introduction of non-phosphorylatable separase mutant rescued chromatid separation in the stable cyclin B2-expressed oocytes. Therefore, the cyclin B2/CDK1 complex conservatively regulates separase activity via inhibitory phosphorylation of separase in both meiosis I and meiosis II of mouse oocyte.

scholarly journals WAPL orchestrates porcine oocyte meiotic progression via control of spindle assembly checkpoint activity

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Changyin Zhou ◽  
Yilong Miao ◽  
Xue Zhang ◽  
Bo Xiong
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Polar Body ◽  
Spindle Assembly ◽  
Protein Levels ◽  
Meiotic Progression ◽  
Oocyte Meiosis ◽  
Chromosome Alignment ◽  
Porcine Oocyte ◽  
Polar Body Extrusion

Abstract Background In mitotic cells, WAPL acts as a cohesin release factor to remove cohesin complexes from chromosome arms during prophase to allow the accurate chromosome segregation in anaphase. However, we have recently documented that Wapl exerts a unique meiotic function in the spindle assembly checkpoint (SAC) control through maintaining Bub3 stability during mouse oocyte meiosis I. Whether this noncanonical function is conserved among species is still unknown. Methods We applied RNAi-based gene silencing approach to deplete WAPL in porcine oocytes, validating the conserved roles of WAPL in the regulation of SAC activity during mammalian oocyte maturation. We also employed immunostaining, immunoblotting and image quantification analyses to test the WAPL depletion on the meiotic progression, spindle assembly, chromosome alignment and dynamics of SAC protein in porcine oocytes. Results We showed that depletion of WAPL resulted in the accelerated meiotic progression by displaying the precocious polar body extrusion and compromised spindle assembly and chromosome alignment. Notably, we observed that the protein level of BUB3 was substantially reduced in WAPL-depleted oocytes, especially at kinetochores. Conclusions Collectively, our data demonstrate that WAPL participates in the porcine oocyte meiotic progression through maintenance of BUB3 protein levels and SAC activity. This meiotic function of WAPL in oocytes is highly conserved between pigs and mice.

scholarly journals Cyclin B3 is specifically required for metaphase to anaphase transition in mouse oocyte meiosis I

2018 ◽  
Author(s):  
Yufei Li ◽  
Leyun Wang ◽  
Linlin Zhang ◽  
Zhengquan He ◽  
Guihai Feng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Chromosome Segregation ◽  
Mammalian Species ◽  
Cell Cycle Control ◽  
Special Role ◽  
List Type ◽  
Oocyte Meiosis ◽  
Cyclin B3 ◽  
Meiosis I

AbstractMeiosis, a cell division to generate gametes for sexual reproduction in eukaryotes, executes a single round of DNA replication and two successive rounds of chromosome segregation [1]. The extraordinary reliability of the meiotic cycle requires the activities of cyclin-dependent kinases (Cdks) associated with specific cyclins [2-4]. Cyclins are the regulatory subunits of protein kinases, which are the main regulators of maturation promoting factor or mitosis promoting factor (MPF) [5, 6] and anaphase-promoting complex/cyclosome (APC/C) [7, 8] in eukaryotic cell division. But how cyclins collaborate to control meiosis is still largely unknown. Cyclin B3 (Ccnb3) shares homology with A- and B-type cyclins [9], and is conserved during higher eukaryote evolution [10-17]. Previous studies have shown that Ccnb3-deleted females are sterile with oocytes unable to complete meiosis I in Drosophila [18], implying that Ccnb3 may have a special role in meiosis. To clarify the function of Ccnb3 in meiosis in mammalian species, we generated Ccnb3 mutant mice by CRISPR/Cas9, and found that Ccnb3 mutation caused female infertility with the failure of metaphase-anaphase transition in meiosis I. Ccnb3 was necessary for APC/C activation to initiate anaphase I, but not required for oocytes maturation, meiosis II progression, or early embryonic development. Our study reveals the differential cell cycle regulation between meiosis I and meiosis II, as well as meiosis between males and females, which shed light on the cell cycle control of meiosis.HighlightsIdentification of a female meiosis-specific cyclin in mouseCyclin B3 is required for metaphase-anaphase transition in oocyte meiosis ICyclin B3 is not essential for oocyte maturation and sister chromosome segregationCyclin B3 is necessary for APC/C activation and MPF kinase activity through Cdk1

scholarly journals Model-guided design of mammalian genetic programs

2021 ◽  
Vol 7 (8) ◽  
pp. eabe9375
Author(s):  
J. J. Muldoon ◽  
V. Kandula ◽  
M. Hong ◽  
P. S. Donahue ◽  
J. D. Boucher ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Computational Models ◽  
Biological Complexity ◽  
Genetic Circuits ◽  
Cellular Functions ◽  
High Performing ◽  
Design Objective ◽  
Complex Functions ◽  
Mammalian Genetic ◽  
Analog Processing

Genetically engineering cells to perform customizable functions is an emerging frontier with numerous technological and translational applications. However, it remains challenging to systematically engineer mammalian cells to execute complex functions. To address this need, we developed a method enabling accurate genetic program design using high-performing genetic parts and predictive computational models. We built multifunctional proteins integrating both transcriptional and posttranslational control, validated models for describing these mechanisms, implemented digital and analog processing, and effectively linked genetic circuits with sensors for multi-input evaluations. The functional modularity and compositional versatility of these parts enable one to satisfy a given design objective via multiple synonymous programs. Our approach empowers bioengineers to predictively design mammalian cellular functions that perform as expected even at high levels of biological complexity.

Sterol and lipid trafficking in mammalian cells

2006 ◽  
Vol 34 (3) ◽  
pp. 335-339 ◽  
Author(s):  
F.R. Maxfield ◽  
M. Mondal
Keyword(s):  
Membrane Trafficking ◽  
Mammalian Cells ◽  
Intracellular Transport ◽  
Vesicular Transport ◽  
Cholesterol Content ◽  
Cellular Functions ◽  
Lipid Trafficking ◽  
Sterol Transport ◽  
A Cell ◽  
Asymmetrically Distributed

The pathways involved in the intracellular transport and distribution of lipids in general, and sterols in particular, are poorly understood. Cholesterol plays a major role in modulating membrane bilayer structure and important cellular functions, including signal transduction and membrane trafficking. Both the overall cholesterol content of a cell, as well as its distribution in specific organellar membranes are stringently regulated. Several diseases, many of which are incurable at present, have been characterized as results of impaired cholesterol transport and/or storage in the cells. Despite their importance, many fundamental aspects of intracellular sterol transport and distribution are not well understood. For instance, the relative roles of vesicular and non-vesicular transport of cholesterol have not yet been fully determined, nor are the non-vesicular transport mechanisms well characterized. Similarly, whether cholesterol is asymmetrically distributed between the two leaflets of biological membranes, and if so, how this asymmetry is maintained, is poorly understood. In this review, we present a summary of the current understanding of these aspects of intracellular trafficking and distribution of lipids, and more specifically, of sterols.

scholarly journals Cytoplasmic dynein participates in meiotic checkpoint inactivation in mouse oocytes by transporting cytoplasmic mitotic arrest-deficient (Mad) proteins from kinetochores to spindle poles

Reproduction ◽  
2007 ◽  
Vol 133 (4) ◽  
pp. 685-695 ◽  
Author(s):  
Dong Zhang ◽  
Shen Yin ◽  
Man-Xi Jiang ◽  
Wei Ma ◽  
Yi Hou ◽  
...  
Keyword(s):  
Spindle Checkpoint ◽  
Germinal Vesicle ◽  
Cytoplasmic Dynein ◽  
Mitotic Arrest ◽  
Checkpoint Proteins ◽  
Meiotic Progression ◽  
Spindle Poles ◽  
Anaphase Onset ◽  
Oocyte Meiosis ◽  
And Function

The present study was designed to investigate the localization and function of cytoplasmic dynein (dynein) during mouse oocyte meiosis and its relationship with two major spindle checkpoint proteins, mitotic arrest-deficient (Mad) 1 and Mad2. Oocytes at various stages during the first meiosis were fixed and immunostained for dynein, Mad1, Mad2, kinetochores, microtubules, and chromosomes. Some oocytes were treated with nocodazole before examination. Anti-dynein antibody was injected into the oocytes at germinal vesicle (GV) stage before the examination of its effects on meiotic progression or Mad1 and Mad2 localization. Results showed that dynein was present in the oocytes at various stages from GV to metaphase II and the locations of Mad1 and Mad2 were associated with dynein’s movement. Both Mad1 and Mad2 had two existing states: one existed in the cytoplasm (cytoplasmic Mad1 or cytoplasmic Mad2), which did not bind to kinetochores, while the other bound to kinetochores (kinetochore Mad1 or kinetochore Mad2). The equilibrium between the two states varied during meiosis and/or in response to the changes of the connection between microtubules and kinetochores. Cytoplasmic Mad1 and Mad2 recruited to chromosomes when the connection between microtubules and chromosomes was destroyed. Inhibition of dynein interferes with cytoplasmic Mad1 and Mad2 transportation from chromosomes to spindle poles, thus inhibits checkpoint silence and delays anaphase onset. These results indicate that dynein may play a role in spindle checkpoint inactivation.

scholarly journals Survivin regulates chromosome segregation by modulating the phosphorylation of Aurora B during porcine oocyte meiosis

Cell Cycle ◽  
2018 ◽  
Vol 17 (21-22) ◽  
pp. 2436-2446 ◽  
Author(s):  
Li Chen ◽  
Tailang Yin ◽  
Zheng-Wen Nie ◽  
Tao Wang ◽  
Ying-Ying Gao ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Aurora B ◽  
Oocyte Meiosis ◽  
Porcine Oocyte

The diverse roles of the Nup93/Nic96 complex proteins – structural scaffolds of the nuclear pore complex with additional cellular functions

2014 ◽  
Vol 395 (5) ◽  
pp. 515-528 ◽  
Author(s):  
Benjamin Vollmer ◽  
Wolfram Antonin
Keyword(s):  
Nuclear Pore Complex ◽  
Nuclear Membrane ◽  
Building Blocks ◽  
Transport Processes ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Cellular Functions ◽  
Complex Assembly ◽  
Essential Function ◽  
Pore Complexes

Abstract Nuclear pore complexes mediate the transport between the cell nucleoplasm and cytoplasm. These 125 MDa structures are among the largest assemblies found in eukaryotes, built from proteins organized in distinct subcomplexes that act as building blocks during nuclear pore complex biogenesis. In this review, we focus on one of these subcomplexes, the Nup93 complex in metazoa and its yeast counterpart, the Nic96 complex. We discuss its essential function in nuclear pore complex assembly as a linker between the nuclear membrane and the central part of the pore and its various roles in nuclear transport processes and beyond.

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