bims-micesi Biomed News
on Mitotic cell signalling
Issue of 2022–12–18
thirteen papers selected by
Valentina Piano, Uniklinik Köln
  1. Kinetochore-catalyzed MCC formation: A structural perspective.
  2. Acquisition of the spindle assembly checkpoint and its modulation by cell fate and cell size in a chordate embryo.
  3. In Vitro Methods to Investigate the Disassembly of the Golgi Ribbon During the G2-M Transition of the Cell Cycle.
  4. STYK1/NOK affects cell cycle late mitosis and directly interacts with anaphase-promoting complex activator CDH1.
  5. Mitotic progression and dual spindle formation caused by spindle association of de novo-formed microtubule-organizing centers in parthenogenetic embryos of Drosophila ananassae.
  6. Fam96b recruits brain-type creatine kinase to fuel mitotic spindle formation.
  7. Insights on the Role of PGRMC1 in Mitotic and Meiotic Cell Division.
  8. CENP-F-dependent DRP1 function regulates APC/C activity during oocyte meiosis I.
  9. The Centrosome Cycle within the Cell Cycle.
  10. Kinesin-5 Eg5 is essential for spindle assembly, chromosome stability and organogenesis in development.
  11. Mechanics and regulation of cytokinetic abscission.
  12. The anaphase promoting complex/cyclosome (APC/C) ubiquitylates histone H2B on the promoter during UbcH10 transactivation.
  13. APC/CCDC20 targets SCFFBL17 to activate replication stress responses in Arabidopsis.
  1. IUBMB Life. 2022 Dec 14.
    Kinetochore-catalyzed MCC formation: A structural perspective.
    Elyse S Fischer.
      The spindle assembly checkpoint (SAC) is a cellular surveillance mechanism that functions to ensure accurate chromosome segregation during mitosis. Macromolecular complexes known as kinetochores, act as the interface of sister chromatid attachment to spindle microtubules. In response to unattached kinetochores, the SAC activates its effector, the mitotic checkpoint complex (MCC), which delays mitotic exit until all sister chromatid pairs have achieved successful attachment to the bipolar mitotic spindle. Formation of the MCC (composed of Mad2, BubR1, Bub3 and Cdc20) is regulated by an Mps1 kinase-dependent phosphorylation signaling cascade which assembles and repositions components of the MCC onto a catalytic scaffold. This scaffold functions to catalyze the conversion of the HORMA-domain protein Mad2 from an "inactive" open-state (O-Mad2) into an "active" closed-Mad2 (C-Mad2), and simultaneous Cdc20 binding. Here, our current understanding of the molecular mechanisms underlying the kinetic barrier to C-Mad2:Cdc20 formation will be reviewed. Recent progress in elucidating the precise molecular choreography orchestrated by the catalytic scaffold to rapidly assemble the MCC will be examined, and unresolved questions will be highlighted. Ultimately, understanding how the SAC rapidly activates the checkpoint not only provides insights into how cells maintain genomic integrity during mitosis, but also provides a paradigm for how cells can utilize molecular switches, including other HORMA domain-containing proteins, to make rapid changes to a cell's physiological state.
    Keywords:  Bub1; Cdc20; Mad1; Mps1; mitotic checkpoint complex; spindle assembly checkpoint
    DOI:  https://doi.org/10.1002/iub.2697
  2. Development. 2022 Dec 13. pii: dev.201145. [Epub ahead of print]
    Acquisition of the spindle assembly checkpoint and its modulation by cell fate and cell size in a chordate embryo.
    Marianne Roca, Lydia Besnardeau, Elisabeth Christians, Alex McDougall, Janet Chenevert, Stefania Castagnetti.
      The spindle assembly checkpoint (SAC) is a surveillance system which preserves genome integrity by delaying anaphase onset until all chromosomes are correctly attached to spindle microtubules. Recruitment of SAC proteins to unattached kinetochores generates an inhibitory signal that prolongs mitotic duration. Chordate embryos are atypical in that spindle defects do not delay mitotic progression during early development, implying that either the SAC is inactive or the cell-cycle target machinery unresponsive. Here we show that in embryos of the chordate Phallusiamammillata the SAC delays mitotic progression from the 8th cleavage divisions. Unattached kinetochores are not recognized by the SAC machinery until the 7th cell cycle when the SAC is acquired. Following acquisition, SAC strength, manifest as the degree of mitotic lengthening induced by spindle perturbations, is specific to different cell types and is modulated by cell size showing similarity to SAC control in early Caenorhabditis elegans embryos. We conclude that SAC acquisition is a process likely specific to chordate embryos, while modulation of SAC efficiency in SAC proficient stages depends on cell fate and cell size similarly to non-chordate embryos.
    Keywords:  Ascidian; Embryo; Kinetochore; Mitosis; SAC acquisition; Spindle assembly checkpoint
    DOI:  https://doi.org/10.1242/dev.201145
  3. Methods Mol Biol. 2023 ;2557 333-347
    In Vitro Methods to Investigate the Disassembly of the Golgi Ribbon During the G2-M Transition of the Cell Cycle.
    Inmaculada Ayala, Antonino Colanzi.
      The Golgi complex is the central hub of the secretory pathway. In mammalian cells, it is formed by stacks of flattened cisternae organized in a continuous membrane system, the Golgi ribbon, located near the centrosome. During G2, the Golgi ribbon is disassembled into isolated stacks that, at the onset of mitosis, are further fragmented into small tubular-vesicular clusters that disperse throughout the cytoplasm. Here, we describe a set of methods to study the Golgi complex in different phases of the cell cycle, drawing attention to reproducing the mitotic Golgi fragmentation to gain knowledge and acquire the skills to study the mechanisms that regulate mitotic Golgi reorganization as well as its biological significance. The investigations based on these assays have been instrumental in understanding that Golgi disassembly is not only a consequence of mitosis but is also required for mitotic entry and cell division.
    Keywords:  Cell cycle regulation; Cell cycle synchronization; Cell permeabilization; Golgi structure; Mitosis
    DOI:  https://doi.org/10.1007/978-1-0716-2639-9_21
  4. Heliyon. 2022 Dec;8(12): e12058
    STYK1/NOK affects cell cycle late mitosis and directly interacts with anaphase-promoting complex activator CDH1.
    Su-Lin Zeng, Suraj S Patel, Mo-Qi Lv, Daphne Zhu, Wen H Shen, Li Liu.
      The novel oncogene STYK1/NOK plays critical roles in cancer development. However, its regulation during cell division is less defined. In this paper, we show that over-expression of STYK1/NOK caused mitotic arrest and cytokinesis defects. The protein level of STYK/NOK fluctuated during the cell cycle, with a peak at mitosis and a quick reduction upon mitotic exit. The cell cycle-related expression pattern of STYK1/NOK resembled the one of aurora kinases and polo-like kinase 1. Depletion of APC3 led to accumulation of STYK1/NOK and to the G2/M arrest. Co-immunoprecipitation experiment demonstrated the direct interaction of STYK1/NOK with CDH1. Overexpression of CDH1 shortened the half-life of STYK1/NOK. The kinase domain, but not the five D boxes, of STYK1/NOK was responsible for the interaction with CDH1. Altogether, our data demonstrated for the first time that STYK1/NOK could affect cell division, probably by directly targeting key components of APC/C such as CDH1 at late mitosis. Current study may provide a vital mechanistic clue for understanding the roles of STYK1/NOK in mitosis and cytokinesis during STYK1NOK mediated genomic instability and oncogenesis.
    Keywords:  APC/C; CDH1; Cell cycle; Protein-protein interaction; STYK1/NOK
    DOI:  https://doi.org/10.1016/j.heliyon.2022.e12058
  5. Genetics. 2022 Dec 14. pii: iyac178. [Epub ahead of print]
    Mitotic progression and dual spindle formation caused by spindle association of de novo-formed microtubule-organizing centers in parthenogenetic embryos of Drosophila ananassae.
    Kazuyuki Hirai, Yoshihiro H Inoue, Muneo Matsuda.
      Facultative parthenogenesis occurs in many animal species that typically undergo sexual reproduction. In Drosophila, such development from unfertilized eggs involves diploidization after completion of meiosis, but the exact mechanism remains unclear. Here we used a laboratory stock of Drosophila ananassae that has been maintained parthenogenetically to cytologically examine the initial events of parthenogenesis. Specifically, we determined whether the requirements for centrosomes and diploidization that are essential for developmental success can be overcome. As a primal deviation from sexually reproducing (i.e., sexual) strains of the same species, free asters emerged from the de novo formation of centrosome-like structures in the cytosol of unfertilized eggs. Those microtubule-organizing centers (MTOCs) had distinct roles in the earliest cycles of parthenogenetic embryos with respect to mitotic progression and arrangement of mitotic spindles. In the first cycle, an anastral bipolar spindle self-assembled around a haploid set of replicated chromosomes. Participation of at least one MTOC in the spindle was necessary for mitotic progression into anaphase. In particular, the first mitosis involving a monastral bipolar spindle resulted in haploid daughter nuclei, one of which was associated with an MTOC whereas the other was not. Remarkably, in the following cycle, biastral and anastral bipolar spindles formed that were frequently arranged in tandem by sharing an aster with bidirectional connections at their central poles. We propose that, for diploidization of haploid nuclei, unfertilized parthenogenetic embryos utilize dual spindles during the second mitosis, as occurs for the first mitosis in normal fertilized eggs.
    Keywords:  acentrosomal spindle poles; diploidization; monastral bipolar spindles; parallel microtubule interactions; syncytial nuclear divisions
    DOI:  https://doi.org/10.1093/genetics/iyac178
  6. Biochim Biophys Acta Mol Cell Res. 2022 Dec 08. pii: S0167-4889(22)00202-6. [Epub ahead of print]1870(2): 119410
    Fam96b recruits brain-type creatine kinase to fuel mitotic spindle formation.
    Xin-Hang Zhang, Xiang-Jun Chen, Yong-Bin Yan.
      Mitosis is a complicated and ordered process with high energy demands and metabolite fluxes. Cytosolic creatine kinase (CK), an enzyme involved in ATP homeostasis, has been shown to be essential to chromosome movement during mitotic anaphase in sea urchin. However, it remains elusive for the molecular mechanism underlying the recruitment of cytosolic CK by the mitotic apparatus. In this study, Fam96b/MIP18, a component of the MMXD complex with a function in Fe/S cluster supply, was identified as a brain-type CK (CKB)-binding protein. The binding of Fam96b with CKB was independent of the presence of CKB substrates and did not interfere with CKB activity. Fam96b was prone to oligomerize via the formation of intermolecular disulfide bonds, while the binding of enzymatically active CKB could modulate Fam96b oligomerization. Oligomerized Fam96b recruited CKB and the MMXD complex to associate with the mitotic spindle. Depletion of Fam96b or CKB by siRNA in the HeLa cells led to mitotic defects, which further resulted in retarded cell proliferation, increased cell death and aberrant cell cycle progression. Rescue experiments indicated that both Fam96b oligomerization and CKB activity were essential to the proper formation of mitotic spindle. These findings suggest that Fam96b may act as a scaffold protein to coordinate the supply and homeostasis of ATP and Fe/S clusters during mitosis.
    Keywords:  ATP homeostasis; Brain-type creatine kinase; Fam96b; Mitosis; Phosphocreatine-creatine kinase shuttle; Spindle apparatus
    DOI:  https://doi.org/10.1016/j.bbamcr.2022.119410
  7. Cancers (Basel). 2022 Nov 23. pii: 5755. [Epub ahead of print]14(23):
    Insights on the Role of PGRMC1 in Mitotic and Meiotic Cell Division.
    Valentina Lodde, Rodrigo Garcia Barros, Laura Terzaghi, Federica Franciosi, Alberto Maria Luciano.
      During mitosis, chromosome missegregation and cytokinesis defects have been recognized as hallmarks of cancer cells. Cytoskeletal elements composing the spindle and the contractile ring and their associated proteins play crucial roles in the faithful progression of mitotic cell division. The hypothesis that PGRMC1, most likely as a part of a yet-to-be-defined complex, is involved in the regulation of spindle function and, more broadly, the cytoskeletal machinery driving cell division is particularly appealing. Nevertheless, more than ten years after the preliminary observation that PGRMC1 changes its localization dynamically during meiotic and mitotic cell division, this field of research has remained a niche and needs to be fully explored. To encourage research in this fascinating field, in this review, we will recap the current knowledge on PGRMC1 function during mitotic and meiotic cell division, critically highlighting the strengths and limitations of the experimental approaches used so far. We will focus on known interacting partners as well as new putative associated proteins that have recently arisen in the literature and that might support current as well as new hypotheses of a role for PGRMC1 in specific spindle subcompartments, such as the centrosome, kinetochores, and the midzone/midbody.
    Keywords:  cell division; cytokinesis; cytoskeleton; meiosis; mitosis; progesterone receptor membrane component 1; spindle
    DOI:  https://doi.org/10.3390/cancers14235755
  8. Nat Commun. 2022 Dec 13. 13(1): 7732
    CENP-F-dependent DRP1 function regulates APC/C activity during oocyte meiosis I.
    Cheng-Jie Zhou, Xing-Yue Wang, Yan-Hua Dong, Dong-Hui Wang, Zhe Han, Xiao-Jie Zhang, Qing-Yuan Sun, John Carroll, Cheng-Guang Liang.
      Chromosome segregation is initiated by cohesin degradation, which is driven by anaphase-promoting complex/cyclosome (APC/C). Chromosome cohesin is removed by activated separase, with the degradation of securin and cyclinB1. Dynamin-related protein 1 (DRP1), a component of the mitochondrial fission machinery, is related to cyclin dynamics in mitosis progression. Here, we show that DRP1 is recruited to the kinetochore by centromeric Centromere protein F (CENP-F) after nuclear envelope breakdown in mouse oocytes. Loss of DRP1 during prometaphase leads to premature cohesin degradation and chromosome segregation. Importantly, acute DRP1 depletion activates separase by initiating cyclinB1 and securin degradation during the metaphase-to-anaphase transition. Finally, we demonstrate that DRP1 is bound to APC2 to restrain the E3 ligase activity of APC/C. In conclusion, DRP1 is a CENP-F-dependent atypical spindle assembly checkpoint (SAC) protein that modulates metaphase-to-anaphase transition by controlling APC/C activity during meiosis I in oocytes.
    DOI:  https://doi.org/10.1038/s41467-022-35461-5
  9. Adv Anat Embryol Cell Biol. 2022 ;235 17-35
    The Centrosome Cycle within the Cell Cycle.
    Heide Schatten.
      The synchronized distribution of centrosomal and genetic materials to the dividing daughter cells is critically important and depends on precisely orchestrated processes on structural and molecular levels. Structural and functional relationships between the nucleus and centrosomes facilitate cellular communication and coordination of cell cycle control and progression which becomes especially important during the transition from interphase to mitosis when synchrony between centrosomes and nuclear events is critical.
    DOI:  https://doi.org/10.1007/978-3-031-20848-5_2
  10. Cell Death Discov. 2022 Dec 13. 8(1): 490
    Kinesin-5 Eg5 is essential for spindle assembly, chromosome stability and organogenesis in development.
    Wen-Xin Yu, Yu-Kun Li, Meng-Fei Xu, Chen-Jie Xu, Jie Chen, Ya-Lan Wei, Zhen-Yu She.
      Chromosome stability relies on bipolar spindle assembly and faithful chromosome segregation during cell division. Kinesin-5 Eg5 is a plus-end-directed kinesin motor protein, which is essential for spindle pole separation and chromosome alignment in mitosis. Heterozygous Eg5 mutations cause autosomal-dominant microcephaly, primary lymphedema, and chorioretinal dysplasia syndrome in humans. However, the developmental roles and cellular mechanisms of Eg5 in organogenesis remain largely unknown. In this study, we have shown that Eg5 inhibition leads to the formation of the monopolar spindle, chromosome misalignment, polyploidy, and subsequent apoptosis. Strikingly, long-term inhibition of Eg5 stimulates the immune responses and the accumulation of lymphocytes in the mouse spleen through the innate and specific immunity pathways. Eg5 inhibition results in metaphase arrest and cell growth inhibition, and suppresses the formation of somite and retinal development in zebrafish embryos. Our data have revealed the essential roles of kinesin-5 Eg5 involved in cell proliferation, chromosome stability, and organogenesis during development. Our findings shed a light on the cellular basis and pathogenesis in microcephaly, primary lymphedema, and chorioretinal dysplasia syndrome of Eg5-mutation-positive patients.
    DOI:  https://doi.org/10.1038/s41420-022-01281-1
  11. Front Cell Dev Biol. 2022 ;10 1046617
    Mechanics and regulation of cytokinetic abscission.
    Virginia Andrade, Arnaud Echard.
      Cytokinetic abscission leads to the physical cut of the intercellular bridge (ICB) connecting the daughter cells and concludes cell division. In different animal cells, it is well established that the ESCRT-III machinery is responsible for the constriction and scission of the ICB. Here, we review the mechanical context of abscission. We first summarize the evidence that the ICB is initially under high tension and explain why, paradoxically, this can inhibit abscission in epithelial cells by impacting on ESCRT-III assembly. We next detail the different mechanisms that have been recently identified to release ICB tension and trigger abscission. Finally, we discuss whether traction-induced mechanical cell rupture could represent an ancient alternative mechanism of abscission and suggest future research avenues to further understand the role of mechanics in regulating abscission.
    Keywords:  ESCRT; abscission; actin; caveolae; cell division; cell mechanics; cytokinesis; myosin II
    DOI:  https://doi.org/10.3389/fcell.2022.1046617
  12. FEBS Lett. 2022 Dec 15.
    The anaphase promoting complex/cyclosome (APC/C) ubiquitylates histone H2B on the promoter during UbcH10 transactivation.
    Puja Chakraborty, Ratnadip Paul, Abhishek Chowdhury, Nayonika Mukherjee, Somsubhra Nath, Susanta Roychoudhury.
      Among various post-translational modifications of histones, ubiquitylation plays a crucial role in transcription regulation. Histone mono-ubiquitylation by RING finger motif-containing ubiquitin ligases is documented in this respect. The RING finger ligases primarily regulate the cell cycle, where the anaphase-promoting complex/cyclosome (APC/C) takes charge as mitotic ubiquitin machinery. Reportedly, APC/C participates in transcriptional activation of the ubiquitin carrier protein UbcH10. However, the ubiquitylation activity of APC/C on the UBCH10 promoter remains elusive. This study shows that APC/C, with its adapter protein Cdc20 catalyses mono-ubiquitylation of Lysine-120 in histone-2B on the UBCH10 promoter. This study also identified a cell-cycle specific pattern of this modification. Finally, APC/C-driven crosstalk of acetylation and ubiquitylation was found operational on UBCH10 trans-regulation. Together, the findings suggest a role for APC/C catalyzed promoter ubiquitylation in managing transcription of cell cycle regulatory genes.
    DOI:  https://doi.org/10.1002/1873-3468.14563
  13. Plant Cell. 2022 Dec 12. pii: koac360. [Epub ahead of print]
    APC/CCDC20 targets SCFFBL17 to activate replication stress responses in Arabidopsis.
    Ting Pan, Shan Gao, Xiaoyu Cui, Lili Wang, Shunping Yan.
      DNA replication stress threatens genome stability and affects plant growth and development. How plants resolve replication stress is poorly understood. The protein kinase WEE1-mediated cell cycle arrest is required for replication stress responses. The E3 ubiquitin ligases Anaphase-promoting complex/cyclosome (APC/C) and Skp1/Cullin 1/F-box (SCF) are essential regulators of the cell cycle. Here, we show that APC/CCDC20 mediates the degradation of SCFFBL17 during replication stress responses in Arabidopsis thaliana. Biochemically, WEE1 interacts with and phosphorylates the APC/C co-activator APC10, which enhances the interaction between F BOX-LIKE17 (FBL17) and CELL DIVISION CYCLE 20 (CDC20), an activator of APC/C. Both APC10 and CDC20 are required for the polyubiquitination and degradation of FBL17. Genetically, silencing CDC20 or APC10 confers plant hypersensitivity to replication stress, which is suppressed by loss of FBL17. Collectively, our study suggests that WEE1 activates APC/C to inhibit FBL17, providing insight into replication stress responses in plants.
    Keywords:  APC/C; DNA replication stress; SCF; WEE1; ubiquitination
    DOI:  https://doi.org/10.1093/plcell/koac360
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