bims-micesi Biomed News
on Mitotic cell signalling
Issue of 2022–04–03
seven papers selected by
Valentina Piano, Max Planck Institute of Molecular Physiology
  1. Annexin A2 and Ahnak control cortical NuMA-dynein localization and mitotic spindle orientation.
  2. Cell division: Naegleria bundles up for mitosis.
  3. Three interacting regions of the Ndc80 and Dam1 complexes support microtubule tip-coupling under load.
  4. Insights Into Mechanisms of Oriented Division From Studies in 3D Cellular Models.
  5. PLK1 controls centriole distal appendage formation and centrobin removal via independent pathways.
  6. Evolution of eukaryotic centromeres by drive and suppression of selfish genetic elements.
  7. The genetics and epigenetics of satellite centromeres.
  1. J Cell Sci. 2022 Apr 01. pii: jcs.259344. [Epub ahead of print]
    Annexin A2 and Ahnak control cortical NuMA-dynein localization and mitotic spindle orientation.
    Aude Pascal, Emmanuel Gallaud, Regis Giet, Christelle Benaud.
      Proper mitotic spindle orientation depends on the correct anchorage of astral microtubules to the cortex. It relies on the remodeling of the cell cortex, a process not fully understood. Annexin A2 (Anx2) is a protein known to be involved in cortical domain remodeling. Here, we report that in early mitosis, Anx2 recruits the scaffold protein Ahnak at the cell cortex facing spindle poles, and the distribution of both proteins is controlled by cell adhesion. Depletion of either protein or impaired cortical Ahnak localization result in delayed anaphase onset and unstable spindle anchoring, which leads to altered spindle orientation. We find that Ahnak is present in a complex with dynein-dynactin. Furthermore, Ahnak and Anx2 are required for dynein and NuMA proper cortical localization and dynamics. We propose that the Ahnak/Anx2 complex influences the cortical organization of the astral microtubule anchoring complex, and thereby mitotic spindle positioning in human cells.
    Keywords:  Ahnak; Annexin A2; Mitosis; Mitotic cortex; Spindle orientation
    DOI:  https://doi.org/10.1242/jcs.259344
  2. Curr Biol. 2022 Mar 28. pii: S0960-9822(22)00186-5. [Epub ahead of print]32(6): R269-R271
    Cell division: Naegleria bundles up for mitosis.
    Amy N Sinclair, Christopher L de Graffenried.
      How well do we understand the range of mechanisms used by eukaryotes for mitosis? A new study in a highly divergent eukaryote shows that unusual tubulin isoforms can create a mitotic spindle exclusively out of microtubule bundles.
    DOI:  https://doi.org/10.1016/j.cub.2022.01.079
  3. J Cell Biol. 2022 May 02. pii: e202107016. [Epub ahead of print]221(5):
    Three interacting regions of the Ndc80 and Dam1 complexes support microtubule tip-coupling under load.
    Rachel L Flores, Zachary E Peterson, Alex Zelter, Michael Riffle, Charles L Asbury, Trisha N Davis.
      Accurate mitosis requires kinetochores to make persistent, load-bearing attachments to dynamic microtubule tips, thereby coupling chromosome movements to tip growth and shortening. This tip-coupling behavior depends on the conserved Ndc80 complex and, in budding yeast, on the Dam1 complex, which bind each other directly via three distinct interacting regions. The functional relevance of these multiple interactions was mysterious. Here we show that interactions between two of these regions support the high rupture strengths that occur when applied force is rapidly increased and also support the stability of tip-coupling when force is held constant over longer durations. The contribution of either of these two regions to tip-coupling is reduced by phosphorylation by Aurora B kinase. The third interaction region makes no apparent contribution to rupture strength, but its phosphorylation by Aurora B kinase specifically decreases the long-term stability of tip-coupling. The specific reduction of long-term stability relative to short-term strength might have important implications for mitotic error correction.
    DOI:  https://doi.org/10.1083/jcb.202107016
  4. Front Cell Dev Biol. 2022 ;10 847801
    Insights Into Mechanisms of Oriented Division From Studies in 3D Cellular Models.
    Federico Donà, Susanna Eli, Marina Mapelli.
      In multicellular organisms, epithelial cells are key elements of tissue organization. In developing tissues, cellular proliferation and differentiation are under the tight regulation of morphogenetic programs, that ensure the correct organ formation and functioning. In these processes, mitotic rates and division orientation are crucial in regulating the velocity and the timing of the forming tissue. Division orientation, specified by mitotic spindle placement with respect to epithelial apico-basal polarity, controls not only the partitioning of cellular components but also the positioning of the daughter cells within the tissue, and hence the contacts that daughter cells retain with the surrounding microenvironment. Daughter cells positioning is important to determine signal sensing and fate, and therefore the final function of the developing organ. In this review, we will discuss recent discoveries regarding the mechanistics of planar divisions in mammalian epithelial cells, summarizing technologies and model systems used to study oriented cell divisions in vitro such as three-dimensional cysts of immortalized cells and intestinal organoids. We also highlight how misorientation is corrected in vivo and in vitro, and how it might contribute to the onset of pathological conditions.
    Keywords:  cysts; epithelial polarity; mitotic spindle orientation; organoids; planar divisions
    DOI:  https://doi.org/10.3389/fcell.2022.847801
  5. J Cell Sci. 2022 Mar 28. pii: jcs.259120. [Epub ahead of print]
    PLK1 controls centriole distal appendage formation and centrobin removal via independent pathways.
    Morgan Le Roux-Bourdieu, Devashish Dwivedi, Daniela Harry, Patrick Meraldi.
      Centrioles are central structural elements of centrosomes and cilia. In human cells daughter centrioles are assembled adjacent to existing centrioles in S-phase and reach their full functionality with the formation of distal and subdistal appendages one-and-a-half cell cycle later, as they exit their second mitosis. Current models postulate that the centriolar protein centrobin acts as placeholder for distal appendage proteins that must be removed to complete distal appendage formation. Here, we investigated in non-transformed human epithelial RPE1 cells the mechanisms controlling centrobin removal and its effect on distal appendage formation. Our data are consistent with a speculative model in which centrobin is removed from older centrioles due to a higher affinity for the newly born daughter centrioles, under the control of the centrosomal kinase Plk1. This removal also depends on the presence of subdistal appendage proteins on the oldest centriole. Removing centrobin, however, is not required for the recruitment of distal appendage proteins, even though this process is equally dependent on Plk1. We conclude that Plk1 kinase regulates centrobin removal and distal appendage formation during centriole maturation via separate pathways.
    Keywords:  Cell cycle; Centrobin; Centrosome; Mitosis; Polo-like kinase 1
    DOI:  https://doi.org/10.1242/jcs.259120
  6. Semin Cell Dev Biol. 2022 Mar 25. pii: S1084-9521(22)00099-4. [Epub ahead of print]
    Evolution of eukaryotic centromeres by drive and suppression of selfish genetic elements.
    Tomohiro Kumon, Michael A Lampson.
      Despite the universal requirement for faithful chromosome segregation, eukaryotic centromeres are rapidly evolving. It is hypothesized that rapid centromere evolution represents an evolutionary arms race between selfish genetic elements that drive, or propagate at the expense of organismal fitness, and mechanisms that suppress fitness costs. Selfish centromere DNA achieves preferential inheritance in female meiosis by recruiting more effector proteins that alter spindle microtubule interaction dynamics. Parallel pathways for effector recruitment are adaptively evolved to suppress functional differences between centromeres. Opportunities to drive are not limited to female meiosis, and selfish transposons, plasmids and B chromosomes also benefit by maximizing their inheritance. Rapid evolution of selfish genetic elements can diversify suppressor mechanisms in different species that may cause hybrid incompatibility.
    Keywords:  Centromere; Evolutionary arms race; Heterochromatin; Kinetochore; Meiotic drive; Selfish genetic elements
    DOI:  https://doi.org/10.1016/j.semcdb.2022.03.026
  7. Genome Res. 2022 Mar 31.
    The genetics and epigenetics of satellite centromeres.
    Paul B Talbert, Steven Henikoff.
      Centromeres, the chromosomal loci where spindle fibers attach during cell division to segregate chromosomes, are typically found within satellite arrays in plants and animals. Satellite arrays have been difficult to analyze because they comprise megabases of tandem head-to-tail highly repeated DNA sequences. Much evidence suggests that centromeres are epigenetically defined by the location of nucleosomes containing the centromere-specific histone H3 variant cenH3, independently of the DNA sequences where they are located; however, the reason that cenH3 nucleosomes are generally found on rapidly evolving satellite arrays has remained unclear. Recently, long-read sequencing technology has clarified the structures of satellite arrays and sparked rethinking of how they evolve, and new experiments and analyses have helped bring both understanding and further speculation about the role these highly repeated sequences play in centromere identification.
    DOI:  https://doi.org/10.1101/gr.275351.121
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