A further function of Ipl1, which also acts to prevent premature chromosome segregation, is to trigger the shedding of the outer kinetochore during meiotic prophase, thereby abolishing the ability of kinetochores to interact with microtubules and promoting assembly of the monopolin complex, which directs kinetochore co-orientation during meiosis I Kim et al. In addition to promoting homolog biorientation, Ark1 is essential for sister kinetochore co-orientation in this organism Hauf et al.
Interestingly, loading of Ark1 to kinetochores relies on S. Ark1 suppresses the attachment of microtubules from opposite poles to binding sites on the same kinetochore merotelic attachment during meiosis I, in a manner dependent on the presence of chiasmata Sakuno et al. During this chiasma-dependent realignment process, Ark1 relocates to the inner centromere on the inside face of the bivalent, away from the site of microtubule attachment Sakuno et al.
This suggests that Ark1 is responsive to tension across homologs, but the molecular mechanism of how this tension is sensed remains completely unknown. Oocyte-specific Aurora C knock-out only leads to subfertility, showing that Aurora C is important for meiotic maturation, but not essential to generate oocytes that can be fertilized Schindler et al.
It is mainly Aurora C that promotes localized CPC activity, chromosome alignment and establishment of kinetochore attachments, required for efficient meiotic progression Balboula and Schindler, , probably due to higher protein stability compared to Aurora B. Maybe in agreement with a higher stability of Aurora C, the kinase is not only detected in the centromere region but also at the axis in between the sister chromatids, in meiosis I.
Aurora C's role at the interchromatid axis is still unknown, but may be related to its role in chromosome condensation Nguyen et al. The kinase counteracts the establishment of stable, end-on attachments of kinetochores to microtubules, probably in all organisms as part of error correction of tension-less attachments. It was proposed that in addition to Mad1 and Mad2 Tunquist et al.
There is enough evidence in mammalian oocytes excluding an essential role for SAC kinases in CSF arrest, both using conditional knock-out mouse models and expression of dominant negative constructs Tsurumi et al. This indicates that beyond potential other functions in meiosis II, such as SAC control, Sgo2 localization, and stabilization of kinetochore-microtubule interactions, SAC kinases are not implicated in establishing or maintaining a CSF arrest. The specificities of the meiotic cell division require adaptation of known regulatory mechanisms that govern somatic cell divisions.
Kinases that are important for mitotic SAC control fulfill important additional roles in meiosis, independent of a functional SAC see Table 1 for a summary of the different roles SAC kinases play in meiosis. Well-known model organisms such as mouse, yeast and Drosophila , emerging model systems, and comparative evolutionary studies will help us to obtain a better picture of the multiple steps regulated by these kinases. Importantly, even though the result of meiosis is the same in all models the generation of haploid cells , details in the molecular pathways ensuring the correct segregation of chromosomes and sister chromatids may vary.
These differences provide key insight that will help us understand the essential parts and targets of each pathway for the generation of euploid gametes.
KW has written most of the part of this review dealing with meiosis in higher organisms, and AM has written most of the part on meiosis in yeast. Both authors have corrected the whole manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The reviewer DF declared a shared affiliation, with no collaboration, with one of the authors, KW, to the handling Editor. Casein kinase 1 coordinates cohesin cleavage, gametogenesis, and exit from M phase in meiosis II. Cell 40, 37— Asghar, A. Bub1 autophosphorylation feeds back to regulate kinetochore docking and promote localized substrate phosphorylation. Synchronized meiosis and recombination in fission yeast: observations with pat diploid cells. Balboula, A.
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Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Materials and Methods. In terms of the machining process, spindles play an important role in a fast production space. For instance, metal lathes are used to cut hard materials.
Along with metals, these machines can also cut plastics, as well as sturdy composite materials. Lathes can be used for milling, which uses rotary cutters to trim away at a piece until it reaches the desired shape. Machines containing spindles can also be used in woodworking, electrical component creation, and manufacturing parts for computers. If so, repair service or a spindle replacement is crucial to prevent disruptions to your operation.
A CNC spindle rebuild entails numerous elements, from analysis of the pieces current condition to performing a test on the newly rebuilt component. For example, reassembling new spindle components must take place in a sterilized environment to prevent dirt and debris from coming in contact with the component. This speeds up degradation and greatly shortens the lifespan of your spindle. You might also consider having your equipment upgraded. Upgrades can increase speed and precision, while also boosting tolerances.
Upgrades may also allow your components to last longer, which means they will be far more cost-effective in the long run. As a leader in spindle design and maintenance, Superior Spindle knows a thing or two about cnc productions. However, not everyone is as comfortable around these technologically advanced systems, even some people who own them. These machines operate by numerical coding, allowing the user to preprogram machine functions.
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Inhibition of RanGTP production in Xenopus egg extracts leads to severe defects in spindle assembly even in the presence of centrosomes Carazo-Salas et al. Other manipulations in different cellular systems meiotic and mitotic also support the view that chromosomes are important determinants for spindle assembly in general Karsenti et al.
However, reports on spindle formation in the absence of chromosomes have challenged this idea Brunet et al. Microtubules become highly dynamic in mitosis. It is conceivable that when two or more dynamic microtubule asters come into proximity in an M-phase cytoplasm, some antiparallel interactions may be established and become stabilized through the recruitment of some mitotic factors.
Spindle-like structures have indeed been reported to form in the absence of chromosomes Faruki et al. This is in apparent contradiction with the Ran gradient model.
However, unlike the finely temporally and spatially controlled process of spindle formation around chromosomes, spindle-like structures formed in the absence of chromosomes arise randomly in the cellular space Brunet et al. Computer simulations have recently been used to analyze theoretically the minimal requirements for the establishment of stable antiparallel interactions between two microtubule asters Nedelec, The results suggest that relatively few components may be sufficient.
Thus, it may not be surprising that in a mitotic cytoplasm two or more microtubule asters may establish antiparallel interactions. One important question is then whether these structures could be as functional as real spindles.
Recently, Drosophila secondary spermatocytes lacking chromosomes have been reported to assemble a spindle and go through anaphase and cytokinesis like wild-type cells Bucciarelli et al. This suggests that except for the obvious lack of chromosome segregation the spindle-like structure that formed retained the other functions attributed to spindles. In fact, a closer look at microtubule organization in these cells suggests that the two microtubule asters nucleated by the centrosomes barely interact.
Because of the space restriction imposed by the cell membrane most microtubules nucleated by the centrosomes can only grow toward the center of the cell and thus adopt a spindle-like topology. However, the density of microtubules in the central region is much lower than in bona fide spindles suggesting that there are no interactions between antiparallel microtubules.
Although the later assembly of the central spindle and cytokinesis could suggest that a spindle had indeed previously assembled, in fact these are most certainly independent events. First, in this meiotic system the spindle checkpoint is nonexistent or very weak Rebollo and Gonzalez, Second, the central spindle does not derive from the spindle itself but forms from newly assembled microtubules that grow in the central cortical region of the cell C. Gonzalez, personal communication. Moreover, using live imaging on dividing spermatocytes, Rebollo et al.
Interestingly, these authors have also shown that spindles can assemble in Drosophila spermatocytes without any contribution from centrosome nucleated microtubules Rebollo et al. Finally, Canman et al.
Therefore, these data suggest that these late events do not depend on the previous formation of a spindle. In summary, although some antiparallel interactions may be established between two or more microtubule asters in an M-phase cytoplasm, chromosomes appear as important determinants to direct spatially the formation of a robust spindle.
During mitosis RanGTP regulates the activity of factors involved in microtubule nucleation, stabilization and organization Wilde and Zheng, ; Zhang et al. These proteins have been proposed to be targets of RanGTP in the spindle assembly pathway Gruss et al. By contrast, the majority of NuMA is bound to the dynein—dynactin complex Merdes et al. The number of proteins regulated by Ran during cell division will probably increase rapidly. Likely candidate factors involved in cell division are those sequestered into the nucleus in interphase and thus interacting with importins.
The microtubule binding capacity of the nuclear KLP kid was recently found to be modulated by Ran and the importins in vitro Trieselmann et al. In addition, other factors may be regulated in a more indirect manner. Wilde et al. A general picture is starting to emerge in which RanGTP coordinates the activities of numerous factors that collectively direct the formation of the spindle around the chromosomes Fig.
However, TPX2 probably remains the best-characterized Ran target. Moreover, many recent data suggest that the regulation of TPX2 is important for several steps in spindle assembly. We will focus on TPX2 in the last part of this review. TPX2 triggers microtubule nucleation and binds to the mitotic kinase Aurora A activating it.
Although TPX2 was first identified as an antigen specific for mitosis Heidebrecht et al. How does TPX2 trigger microtubule assembly? TPX2 behaves as a microtubule associated protein MAP in all biochemical assays and it colocalizes with spindle microtubules in M-phase in vivo and in vitro Heidebrecht et al. However, TPX2 does not stabilize microtubules like other MAPs but probably plays a yet poorly understood role in the early steps of microtubule nucleation Gruss et al.
In fact, bacterially expressed TPX2 can initiate microtubule polymerization in a solution of pure tubulin, an activity regulated by importins Schatz et al. Together, these data indicate strongly that an essential early role of TPX2 is to promote microtubule assembly in the vicinity of chromosomes. Accordingly, TPX2 has been found to be crucial for spindle formation in Xenopus egg extracts and in tissue culture cells Gruss et al. These studies indicate that microtubule assembly induced by TPX2 around the chromosomes is a general requirement for spindle assembly—a conclusion in sharp contrast with the idea that two centrosomal asters are sufficient to organize a spindle see Spindle assembly without chromosomes?
Factors proposed to be regulated by RanGTP during mitosis and their role in spindle assembly. TPX2 is released from the importins and triggers microtubule nucleation. B Organization: microtubules assembled around the chromosomes coalesce and start to organize. C Pole formation: microtubule minus ends focus into spindle poles. TPX2 may also play a role in this process.
TPX2 accumulates at the poles of metaphase spindles in a dynein—dynactin-dependent way. This localization does not depend on RanGTP because TPX2 accumulates at the center of microtubule asters induced in Xenopus egg extracts by addition of centrosomes, or agents like taxol or DMSO and binds to pure microtubules in the presence of importins Wittmann et al. The precise mechanism involved in this localization is still unclear.
In contrast to NuMA Merdes et al. In any case, the spindle pole localization of TPX2 may be important functionally because TPX2 is required for spindle pole integrity Wittmann et al. The function of TPX2 at spindle poles could also be related to its targeting activities. Interestingly, this interaction leads to the activation of the kinase and, in turn, the phosphorylation of TPX2 by Aurora A Eyers et al.
Structural and biochemical studies have helped to understand the precise mechanism by which TPX2 activates the kinase Bayliss et al. The binding of a short NH 2 -terminal sequence of TPX2 to the catalytic domain of Aurora A locks the kinase into an active conformation. First, it positions the activation segment into a more favorable conformation for substrate binding and second by inducing the swinging of a critical phosphorylated residue into a buried position protecting it from dephosphorylation by PP1 and thus inactivation Bayliss et al.
In contrast, it is not clear whether and how Aurora A—mediated phosphorylation of TPX2 affects its activities. In any case, the RanGTP-dependent microtubule assembly activity of TPX2 as well as its RanGTP-mediated interaction with Aurora A that leads to the activation of the kinase reveal important mechanisms by which RanGTP can control directly and indirectly the activity of factors required for spindle assembly.
The central role of Ran in spindle formation reflects the general importance of the regulation of nuclear proteins in this process. In fact, nuclear proteins, all set free early in mitosis upon nuclear envelope breakdown, are involved at all stages of M-phase. Thus, it will be interesting to see whether and how Ran works to regulate the accessibility of nuclear proteins for late functions in cell division like chromosome segregation and cytokinesis.
National Center for Biotechnology Information , U. Journal List J Cell Biol v. J Cell Biol. Oliver J. Gruss 1 and Isabelle Vernos 2. Author information Article notes Copyright and License information Disclaimer.
Fax: LBME sonrev ; or ed. Received Dec 15; Accepted Aug This article has been cited by other articles in PMC. Abstract Recent work has provided new insights into the mechanism of spindle assembly. General mechanism of Ran action during the cell cycle: a small protein with many tricks The function of Ran in nucleocytoplasmic transport during interphase has been extensively studied.
A gradient of RanGTP in mitosis? Spindle assembly without chromosomes? Targets of Ran during mitosis During mitosis RanGTP regulates the activity of factors involved in microtubule nucleation, stabilization and organization Wilde and Zheng, ; Zhang et al. Table I.
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