scholarly journals Klp2 and Ase1 synergize to maintain meiotic spindle stability during metaphase I

2020 ◽  
Author(s):  
Fan Zheng ◽  
Fenfen Dong ◽  
Shuo Yu ◽  
Tianpeng Li ◽  
Yanze Jian ◽  
...  

ABSTRACTThe spindle apparatus segregates bi-oriented sister chromatids during mitosis but mono-oriented homologous chromosomes during meiosis I. It has remained unclear if similar molecular mechanisms operate to regulate spindle dynamics during mitosis and meiosis I. Here, we employed live-cell microscopy to compare the spindle dynamics of mitosis and meiosis I in fission yeast cells and demonstrated that the conserved kinesin-14 motor Klp2 plays a specific role in maintaining metaphase spindle length during meiosis I, but not during mitosis. Moreover, the maintenance of metaphase spindle stability during meiosis I requires the synergism between Klp2 and the conserved microtubule crosslinker Ase1 as the absence of both proteins causes exacerbated defects in metaphase spindle stability. The synergism is not necessary for regulating mitotic spindle dynamics. Hence, our work reveals a new molecular mechanism underlying meiotic spindle dynamics and provides insights into understanding differential regulation of meiotic and mitotic events.

2020 ◽  
Vol 295 (38) ◽  
pp. 13287-13298
Author(s):  
Fan Zheng ◽  
Fenfen Dong ◽  
Shuo Yu ◽  
Tianpeng Li ◽  
Yanze Jian ◽  
...  

The spindle apparatus segregates bi-oriented sister chromatids during mitosis but mono-oriented homologous chromosomes during meiosis I. It has remained unclear if similar molecular mechanisms operate to regulate spindle dynamics during mitosis and meiosis I. Here, we employed live-cell microscopy to compare the spindle dynamics of mitosis and meiosis I in fission yeast cells and demonstrated that the conserved kinesin-14 motor Klp2 plays a specific role in maintaining metaphase spindle length during meiosis I but not during mitosis. Moreover, the maintenance of metaphase spindle stability during meiosis I requires the synergism between Klp2 and the conserved microtubule cross-linker Ase1, as the absence of both proteins causes exacerbated defects in metaphase spindle stability. The synergism is not necessary for regulating mitotic spindle dynamics. Hence, our work reveals a new molecular mechanism underlying meiotic spindle dynamics and provides insights into understanding differential regulation of meiotic and mitotic events.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3359
Author(s):  
Dimitris Liakopoulos

In the yeast Saccharomyces cerevisiae DNA replication and spindle assembly can overlap. Therefore, signaling mechanisms modulate spindle dynamics in order to ensure correct timing of chromosome segregation relative to genome duplication, especially when replication is incomplete or the DNA becomes damaged. This review focuses on the molecular mechanisms that coordinate DNA replication and spindle dynamics, as well as on the role of spindle-dependent forces in DNA repair. Understanding the coupling between genome duplication and spindle function in yeast cells can provide important insights into similar processes operating in other eukaryotic organisms, including humans.


2011 ◽  
Vol 39 (5) ◽  
pp. 1191-1196 ◽  
Author(s):  
Alistair N. Hume ◽  
Miguel C. Seabra

Advances in live-cell microscopy have revealed the extraordinarily dynamic nature of intracellular organelles. Moreover, movement appears to be critical in establishing and maintaining intracellular organization and organellar and cellular function. Motility is regulated by the activity of organelle-associated motor proteins, kinesins, dyneins and myosins, which move cargo along polar MT (microtubule) and actin tracks. However, in most instances, the motors that move specific organelles remain mysterious. Over recent years, pigment granules, or melanosomes, within pigment cells have provided an excellent model for understanding the molecular mechanisms by which motor proteins associate with and move intracellular organelles. In the present paper, we discuss recent discoveries that shed light on the mechanisms of melanosome transport and highlight future prospects for the use of pigment cells in unravelling general molecular mechanisms of intracellular transport.


1936 ◽  
Vol 121 (823) ◽  
pp. 290-300 ◽  

Triploid organisms have three homologous chromosomes of each kind instead of the two of diploids. The regular mechanism of heredity fails in these circumstances. The triploid is incapable of breeding true by sexual reproduction. But the way in which it carries out the process of chromosome pairing and segregation is of great significance. The processes take place in normal series, but the relationships they establish are abnormal. A triploid thus provides a natural experiment, with the diploid of its own species as a control for one variable, and with triploids of different species as controls for others. In Tulipa and Hyacinthus I have made use of this experiment for inducing the principles of the external mechanics of chromosomes during the prophase of meiosis. I have inferred from them the relationships between the forces working in mitosis and meiosis. The triploid forms of various Fritillaria species make it possible to test the principles of metaphase mechanics induced from observations on structural hybrids and other polyploids (Darlington, 1932, b , and 1933, c ) as well as from the exceptional behaviour in the diploid species of Fritillaria already discussed.


2018 ◽  
Author(s):  
Luciana Previato de Almeida ◽  
Jared M. Evatt ◽  
Hoa H. Chuong ◽  
Emily L. Kurdzo ◽  
Craig A. Eyster ◽  
...  

ABSTRACTFaithful chromosome segregation during meiosis I depends upon the formation of connections between homologous chromosomes. Crossovers between homologs connect the partners allowing them to attach to the meiotic spindle as a unit, such that they migrate away from one another at anaphase I. Homologous partners also become connected by pairing of their centromeres in meiotic prophase. This centromere pairing can promote proper segregation at anaphase I of partners that have failed to become joined by a crossover. Centromere pairing is mediated by synaptonemal complex (SC) proteins that persist at the centromere when the SC disassembles. Here, using mouse spermatocyte and yeast model systems, we tested the role of shugoshin in promoting meiotic centromere pairing by protecting centromeric synaptonemal components from disassembly. The results show that shugoshin protects centromeric SC in meiotic prophase and, in anaphase, promotes the proper segregation of partner chromosomes that are not linked by a crossover.SIGNIFICANCEMeiotic crossovers form a connection between homologous chromosomes that allows them to attach to the spindle as a single unit in meiosis I. In humans, failures in this process are a leading cause of aneuploidy. A recently described process, called centromere pairing, can also help connect meiotic chromosome partners in meiosis. Homologous chromosomes become tightly joined by a structure called the synaptonemal complex (SC) in meiotic prophase. After the SC disassembles, persisting SC proteins at the centromeres mediate their pairing. Here, studies in mouse spermatocytes and yeast are used to show that the shugoshin protein helps SC components persist at centromeres and helps centromere pairing promote the proper segregation of yeast chromosomes that fail to become tethered by crossovers.


2019 ◽  
Vol 4 ◽  
pp. 29 ◽  
Author(s):  
Stefan Galander ◽  
Rachael E. Barton ◽  
David A. Kelly ◽  
Adèle L. Marston

Background: Meiosis produces gametes through two successive nuclear divisions, meiosis I and meiosis II. In contrast to mitosis and meiosis II, where sister chromatids are segregated, during meiosis I, homologous chromosomes are segregated. This requires the monopolar attachment of sister kinetochores and the loss of cohesion from chromosome arms, but not centromeres, during meiosis I. The establishment of both sister kinetochore mono-orientation and cohesion protection rely on the budding yeast meiosis I-specific Spo13 protein, the functional homolog of fission yeast Moa1 and mouse MEIKIN. Methods: Here we investigate the effects of loss of SPO13 on cohesion during meiosis I using a live-cell imaging approach. Results: Unlike wild type, cells lacking SPO13 fail to maintain the meiosis-specific cohesin subunit, Rec8, at centromeres and segregate sister chromatids to opposite poles during anaphase I. We show that the cohesin-destabilizing factor, Wpl1, is not primarily responsible for the loss of cohesion during meiosis I. Instead, premature loss of centromeric cohesin during anaphase I in spo13Δ cells relies on separase-dependent cohesin cleavage. Further, cohesin loss in spo13Δ anaphase I cells is blocked by forcibly tethering the regulatory subunit of protein phosphatase 2A, Rts1, to Rec8. Conclusions: Our findings indicate that separase-dependent cleavage of phosphorylated Rec8 causes premature cohesin loss in spo13Δ cells.


2010 ◽  
Vol 191 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Elisa Dultz ◽  
Jan Ellenberg

In metazoa, new nuclear pore complexes (NPCs) form at two different cell cycle stages: at the end of mitosis concomitant with the reformation of the nuclear envelope and during interphase. However, the mechanisms of these assembly processes may differ. In this study, we apply high resolution live cell microscopy to analyze the dynamics of single NPCs in living mammalian cells during interphase. We show that nuclear growth and NPC assembly are correlated and occur at a constant rate throughout interphase. By analyzing the kinetics of individual NPC assembly events, we demonstrate that they are initiated by slow accumulation of the membrane nucleoporin Pom121 followed by the more rapid association of the soluble NPC subcomplex Nup107–160. This inverse order of recruitment and the overall much slower kinetics compared with postmitotic NPC assembly support the conclusion that the two processes occur by distinct molecular mechanisms.


2019 ◽  
Vol 116 (19) ◽  
pp. 9417-9422 ◽  
Author(s):  
Luciana Previato de Almeida ◽  
Jared M. Evatt ◽  
Hoa H. Chuong ◽  
Emily L. Kurdzo ◽  
Craig A. Eyster ◽  
...  

Faithful chromosome segregation during meiosis I depends upon the formation of connections between homologous chromosomes. Crossovers between homologs connect the partners, allowing them to attach to the meiotic spindle as a unit, such that they migrate away from one another at anaphase I. Homologous partners also become connected by pairing of their centromeres in meiotic prophase. This centromere pairing can promote proper segregation at anaphase I of partners that have failed to become joined by a crossover. Centromere pairing is mediated by synaptonemal complex (SC) proteins that persist at the centromere when the SC disassembles. Here, using mouse spermatocyte and yeast model systems, we tested the role of shugoshin in promoting meiotic centromere pairing by protecting centromeric synaptonemal components from disassembly. The results show that shugoshin protects the centromeric SC in meiotic prophase and, in anaphase, promotes the proper segregation of partner chromosomes that are not linked by a crossover.


2016 ◽  
Vol 27 (3) ◽  
pp. 572-587 ◽  
Author(s):  
Jing He ◽  
Jennifer L. Johnson ◽  
Jlenia Monfregola ◽  
Mahalakshmi Ramadass ◽  
Kersi Pestonjamasp ◽  
...  

The molecular mechanisms that regulate late endosomal maturation and function are not completely elucidated, and direct evidence of a calcium sensor is lacking. Here we identify a novel mechanism of late endosomal maturation that involves a new molecular interaction between the tethering factor Munc13-4, syntaxin 7, and VAMP8. Munc13-4 binding to syntaxin 7 was significantly increased by calcium. Colocalization of Munc13-4 and syntaxin 7 at late endosomes was demonstrated by high-resolution and live-cell microscopy. Munc13-4–deficient cells show increased numbers of significantly enlarged late endosomes, a phenotype that was mimicked by the fusion inhibitor chloroquine in wild-type cells and rescued by expression of Munc13-4 but not by a syntaxin 7–binding–deficient mutant. Late endosomes from Munc13-4-KO neutrophils show decreased degradative capacity. Munc13-4–knockout neutrophils show impaired endosomal-initiated, TLR9-dependent signaling and deficient TLR9-specific CD11b up-regulation. Thus we present a novel mechanism of late endosomal maturation and propose that Munc13-4 regulates the late endocytic machinery and late endosomal–associated innate immune cellular functions.


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