Chromokinesins: localization-dependent functions and regulation during cell division

2011 ◽  
Vol 39 (5) ◽  
pp. 1154-1160 ◽  
Author(s):  
David Vanneste ◽  
Vanessa Ferreira ◽  
Isabelle Vernos
Keyword(s):  
Cell Division ◽  
Molecular Motors ◽  
Current Knowledge ◽  
Spindle Assembly ◽  
Dynamic Structure ◽  
Spindle Pole ◽  
Dependent Manner ◽  
Ki 67 ◽  
Balance Of Forces ◽  
Chromosome Movements

The bipolar spindle is a highly dynamic structure that assembles transiently around the chromosomes and provides the mechanical support and the forces required for chromosome segregation. Spindle assembly and chromosome movements rely on the regulation of microtubule dynamics and a fine balance of forces exerted by various molecular motors. Chromosomes are themselves central players in spindle assembly. They generate a RanGTP gradient that triggers microtubule nucleation and stabilization locally and they interact dynamically with the microtubules through motors targeted to the chromatin. We have previously identified and characterized two of these so-called chromokinesins: Xkid (kinesin 10) and Xklp1 (kinesin 4). More recently, we found that Hklp2/kif15 (kinesin 12) is targeted to the chromosomes through an interaction with Ki-67 in human cells and is therefore a novel chromokinesin. Hklp2 also associates with the microtubules specifically during mitosis, in a TPX2 (targeting protein for Xklp2)-dependent manner. We have shown that Hklp2 participates in spindle pole separation and in the maintenance of spindle bipolarity in metaphase. To better understand the function of Hklp2, we have performed a detailed domain analysis. Interestingly, from its positioning on the chromosome arms, Hklp2 seems to restrict spindle pole separation. In the present review, we summarize the current knowledge of the function and regulation of the different kinesins associated with chromosome arms during cell division, including Hklp2 as a novel member of this so-called chromokinesin family.

scholarly journals The mechanism of spindle assembly

2004 ◽  
Vol 166 (7) ◽  
pp. 949-955 ◽  
Author(s):  
Oliver J. Gruss ◽  
Isabelle Vernos
Keyword(s):  
Cell Division ◽  
Recent Work ◽  
Current Knowledge ◽  
Spindle Assembly ◽  
Small Gtpase ◽  
Multiple Roles ◽  
Mitotic Chromosomes ◽  
Downstream Targets ◽  
Gtpase Ran

Recent work has provided new insights into the mechanism of spindle assembly. Growing evidence supports a model in which the small GTPase Ran plays a central role in this process. Here, we examine the evidence for the existence of a RanGTP gradient around mitotic chromosomes and some controversial data on the role that chromosomes play in spindle assembly. We review the current knowledge on the Ran downstream targets for spindle assembly and we focus on the multiple roles of TPX2, one of the targets of RanGTP during cell division.

scholarly journals Poleward transport of Eg5 by dynein–dynactin in Xenopus laevis egg extract spindles

2008 ◽  
Vol 182 (4) ◽  
pp. 715-726 ◽  
Author(s):  
Marianne Uteng ◽  
Christian Hentrich ◽  
Kota Miura ◽  
Peter Bieling ◽  
Thomas Surrey
Keyword(s):  
Cell Division ◽  
Xenopus Laevis ◽  
Molecular Motors ◽  
Motor Proteins ◽  
Motor Protein ◽  
Spindle Assembly ◽  
Cross Linking ◽  
Motor Movement ◽  
Spindle Poles ◽  
Egg Extract

Molecular motors are required for spindle assembly and maintenance during cell division. How motors move and interact inside spindles is unknown. Using photoactivation and photobleaching, we measure mitotic motor movement inside a dynamic spindle. We find that dynein–dynactin transports the essential motor Eg5 toward the spindle poles in Xenopus laevis egg extract spindles, revealing a direct interplay between two motors of opposite directionality. This transport occurs throughout the spindle except at the very spindle center and at the spindle poles, where Eg5 remains stationary. The variation of Eg5 dynamics with its position in the spindle is indicative of position-dependent functions of this motor protein. Our results suggest that Eg5 drives microtubule flux by antiparallel microtubule sliding in the spindle center, whereas the dynein-dependent concentration of Eg5 outside the spindle center could contribute to parallel microtubule cross-linking. These results emphasize the importance of spatially differentiated functions of motor proteins and contribute to our understanding of spindle organization.

scholarly journals Spatiotemporal regulations of Wee1 at the G2/M transition

2011 ◽  
Vol 22 (5) ◽  
pp. 555-569 ◽  
Author(s):  
Hirohisa Masuda ◽  
Chii Shyang Fong ◽  
Chizuru Ohtsuki ◽  
Tokuko Haraguchi ◽  
Yasushi Hiraoka
Keyword(s):  
Feedback Loop ◽  
Kinase Activity ◽  
Spindle Pole Body ◽  
Spindle Assembly ◽  
Spindle Pole ◽  
Cyclin B ◽  
Dependent Manner ◽  
Mitotic Entry ◽  
G2 Phase ◽  
Cdc2 Activity

Wee1 is a protein kinase that negatively regulates mitotic entry in G2 phase by suppressing cyclin B–Cdc2 activity, but its spatiotemporal regulations remain to be elucidated. We observe the dynamic behavior of Wee1 in Schizosaccharomyces pombe cells and manipulate its localization and kinase activity to study its function. At late G2, nuclear Wee1 efficiently suppresses cyclin B–Cdc2 around the spindle pole body (SPB). During the G2/M transition when cyclin B–Cdc2 is highly enriched at the SPB, Wee1 temporally accumulates at the nuclear face of the SPB in a cyclin B–Cdc2-dependent manner and locally suppresses both cyclin B–Cdc2 activity and spindle assembly to counteract a Polo kinase–dependent positive feedback loop. Then Wee1 disappears from the SPB during spindle assembly. We propose that regulation of Wee1 localization around the SPB during the G2/M transition is important for proper mitotic entry and progression.

scholarly journals Unrestrained Spindle Elongation during Recovery from Spindle Checkpoint Activation in cdc15-2 Cells Results in Mis-Segregation of Chromosomes

2010 ◽  
Vol 21 (14) ◽  
pp. 2384-2398 ◽  
Author(s):  
Chuan Chung Chai ◽  
Ee Mei Teh ◽  
Foong May Yeong
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Checkpoint ◽  
Spindle Assembly ◽  
Spindle Pole ◽  
Checkpoint Activation ◽  
Sister Chromatids ◽  
Spindle Pole Bodies ◽  
Balance Of Forces ◽  
Spindle Elongation ◽  
Pulling Force

During normal metaphase in Saccharomyces cerevisiae, chromosomes are captured at the kinetochores by microtubules emanating from the spindle pole bodies at opposite poles of the dividing cell. The balance of forces between the cohesins holding the replicated chromosomes together and the pulling force from the microtubules at the kinetochores result in the biorientation of the sister chromatids before chromosome segregation. The absence of kinetochore–microtubule interactions or loss of cohesion between the sister chromatids triggers the spindle checkpoint which arrests cells in metaphase. We report here that an MEN mutant, cdc15-2, though competent in activating the spindle assembly checkpoint when exposed to Noc, mis-segregated chromosomes during recovery from spindle checkpoint activation. cdc15-2 cells arrested in Noc, although their Pds1p levels did not accumulate as well as in wild-type cells. Genetic analysis indicated that Pds1p levels are lower in a mad2Δ cdc15-2 and bub2Δ cdc15-2 double mutants compared with the single mutants. Chromosome mis-segregation in the mutant was due to premature spindle elongation in the presence of unattached chromosomes, likely through loss of proper control on spindle midzone protein Slk19p and kinesin protein, Cin8p. Our data indicate that a slower rate of transition through the cell division cycle can result in an inadequate level of Pds1p accumulation that can compromise recovery from spindle assembly checkpoint activation.

scholarly journals TheSaccharomyces cerevisiaeSpindle Pole Body Is a Dynamic Structure

2003 ◽  
Vol 14 (8) ◽  
pp. 3494-3505 ◽  
Author(s):  
Tennessee J. Yoder ◽  
Chad G. Pearson ◽  
Kerry Bloom ◽  
Trisha N. Davis
Keyword(s):  
Cell Cycle ◽  
Spindle Pole Body ◽  
Dynamic Structure ◽  
Spindle Pole ◽  
G1 Arrest ◽  
Dependent Manner ◽  
Dynamic Features ◽  
Pole Body ◽  
Dependent Growth ◽  
Cycle Dependent

During spindle pole body (SPB) duplication, the new SPB is assembled at a distinct site adjacent to the old SPB. Using quantitative fluorescence methods, we studied the assembly and dynamics of the core structural SPB component Spc110p. The SPB core exhibits both exchange and growth in a cell cycle-dependent manner. During G1/S phase, the old SPB exchanges ∼50% of old Spc110p for new Spc110p. In G2 little Spc110p is exchangeable. Thus, Spc110p is dynamic during G1/S and becomes stable during G2. The SPB incorporates additional Spc110p in late G2 and M phases; this growth is followed by reduction in the next G1. Spc110p addition to the SPBs (growth) also occurs in response to G2 and mitotic arrests but not during a G1 arrest. Our results reveal several dynamic features of the SPB core: cell cycle-dependent growth and reduction, growth in response to cell cycle arrests, and exchange of Spc110p during SPB duplication. Moreover, rather than being considered a conservative or dispersive process, the assembly of Spc110p into the SPB is more readily considered in terms of growth and exchange.

Spindle scaling mechanisms

2020 ◽  
Vol 64 (2) ◽  
pp. 383-396
Author(s):  
Lara K. Krüger ◽  
Phong T. Tran
Keyword(s):  
Cell Size ◽  
Spindle Assembly ◽  
Dependent Manner ◽  
Post Translational Modification ◽  
Size Dependent ◽  
A Cell ◽  
Chromosome Separation ◽  
Spindle Elongation ◽  
Protein Gradients ◽  
Spindle Structure

Abstract The mitotic spindle robustly scales with cell size in a plethora of different organisms. During development and throughout evolution, the spindle adjusts to cell size in metazoans and yeast in order to ensure faithful chromosome separation. Spindle adjustment to cell size occurs by the scaling of spindle length, spindle shape and the velocity of spindle assembly and elongation. Different mechanisms, depending on spindle structure and organism, account for these scaling relationships. The limited availability of critical spindle components, protein gradients, sequestration of spindle components, or post-translational modification and differential expression levels have been implicated in the regulation of spindle length and the spindle assembly/elongation velocity in a cell size-dependent manner. In this review, we will discuss the phenomenon and mechanisms of spindle length, spindle shape and spindle elongation velocity scaling with cell size.

scholarly journals Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

2021 ◽  
Vol 22 (15) ◽  
pp. 8117
Author(s):  
Nunzia D’Onofrio ◽  
Elisa Martino ◽  
Luigi Mele ◽  
Antonino Colloca ◽  
Martina Maione ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Protein Levels

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.

scholarly journals Volatile 1-octanol of tea (Camellia sinensis L.) fuels cell division and indole-3-acetic acid production in phylloplane isolate Pseudomonas sp. NEEL19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Poovarasan Neelakandan ◽  
Chiu-Chung Young ◽  
Asif Hameed ◽  
Yu-Ning Wang ◽  
Kui-Nuo Chen ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Cell Division ◽  
Petri Dish ◽  
Gas Chromatography Mass Spectrometry ◽  
Dependent Manner ◽  
Tea Leaves ◽  
Acetic Acid Production ◽  
Iaa Production ◽  
Solvent Tolerant ◽  
Indole 3 Acetic Acid

AbstractTea leaves possess numerous volatile organic compounds (VOC) that contribute to tea’s characteristic aroma. Some components of tea VOC were known to exhibit antimicrobial activity; however, their impact on bacteria remains elusive. Here, we showed that the VOC of fresh aqueous tea leaf extract, recovered through hydrodistillation, promoted cell division and tryptophan-dependent indole-3-acetic acid (IAA) production in Pseudomonas sp. NEEL19, a solvent-tolerant isolate of the tea phylloplane. 1-octanol was identified as one of the responsible volatiles stimulating cell division, metabolic change, swimming motility, putative pili/nanowire formation and IAA production, through gas chromatography-mass spectrometry, microscopy and partition petri dish culture analyses. The bacterial metabolic responses including IAA production increased under 1-octanol vapor in a dose-dependent manner, whereas direct-contact in liquid culture failed to elicit such response. Thus, volatile 1-octanol emitting from tea leaves is a potential modulator of cell division, colonization and phytohormone production in NEEL19, possibly influencing the tea aroma.

scholarly journals Advanced maternal age perturbs mouse embryo development and alters the phenotype of derived embryonic stem cells

2021 ◽  
pp. 1-11
Author(s):  
Pooja Khurana ◽  
Neil R. Smyth ◽  
Bhavwanti Sheth ◽  
Miguel A. Velazquez ◽  
Judith J. Eckert ◽  
...  
Keyword(s):  
Maternal Age ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Advanced Maternal Age ◽  
Preimplantation Embryos ◽  
Dependent Manner ◽  
Ki 67 ◽  
Altered Expression ◽  
Developmental Potential ◽  
Developmental Mechanisms

Abstract Advanced maternal age (AMA) is known to reduce fertility, increases aneuploidy in oocytes and early embryos and leads to adverse developmental consequences which may associate with offspring lifetime health risks. However, investigating underlying effects of AMA on embryo developmental potential is confounded by the inherent senescence present in maternal body systems further affecting reproductive success. Here, we describe a new model for the analysis of early developmental mechanisms underlying AMA by the derivation and characterisation of mouse embryonic stem cell (mESC-like) lines from naturally conceived embryos. Young (7–8 weeks) and Old (7–8 months) C57BL/6 female mice were mated with young males. Preimplantation embryos from Old dams displayed developmental retardation in blastocyst morphogenesis. mESC lines established from these blastocysts using conventional techniques revealed differences in genetic, cellular and molecular criteria conserved over several passages in the standardised medium. mESCs from embryos from AMA dams displayed increased incidence of aneuploidy following Giemsa karyotyping compared with those from Young dams. Moreover, AMA caused an altered pattern of expression of pluripotency markers (Sox2, OCT4) in mESCs. AMA further diminished mESC survival and proliferation and reduced the expression of cell proliferation marker, Ki-67. These changes coincided with altered expression of the epigenetic marker, Dnmt3a and other developmental regulators in a sex-dependent manner. Collectively, our data demonstrate the feasibility to utilise mESCs to reveal developmental mechanisms underlying AMA in the absence of maternal senescence and with reduced animal use.

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