bims-micesi Biomed News
on Mitotic cell signalling
Issue of 2023–03–05
nine papers selected by
Valentina Piano, Uniklinik Köln
  1. Mitotic outcomes and errors in fibrous environments.
  2. Adaptation to spindle assembly checkpoint inhibition through the selection of specific aneuploidies.
  3. Dynein at the kinetochore.
  4. TPX2 Amplification-Driven Aberrant Mitosis in Culture Adapted Human Embryonic Stem Cells with gain of 20q11.21.
  5. Mechanisms of Nuclear Pore Complex disassembly by the mitotic Polo-Like Kinase 1 (PLK-1) in C. elegans embryos.
  6. Shugoshin Regulates Cohesin, Kinetochore-Microtubule Attachments, and Chromosomal Instability.
  7. The restriction of calcium influx in metaphase and post-metaphase stages of cell division revealed by imaging secondary ion mass spectrometry (SIMS).
  8. Rice kinesin-related protein STD1 and microtubule-associated protein MAP65-5 cooperatively control microtubule bundling.
  9. Cannabinoid regulation of neurons in the dentate gyrus during epileptogenesis. Role of CB1R-associated proteins and downstream pathways.
  1. Proc Natl Acad Sci U S A. 2023 Mar 07. 120(10): e2120536120
    Mitotic outcomes and errors in fibrous environments.
    Aniket Jana, Apurba Sarkar, Haonan Zhang, Atharva Agashe, Ji Wang, Raja Paul, Nir S Gov, Jennifer G DeLuca, Amrinder S Nain.
      During mitosis, cells round up and utilize the interphase adhesion sites within the fibrous extracellular matrix (ECM) as guidance cues to orient the mitotic spindles. Here, using suspended ECM-mimicking nanofiber networks, we explore mitotic outcomes and error distribution for various interphase cell shapes. Elongated cells attached to single fibers through two focal adhesion clusters (FACs) at their extremities result in perfect spherical mitotic cell bodies that undergo significant 3-dimensional (3D) displacement while being held by retraction fibers (RFs). Increasing the number of parallel fibers increases FACs and retraction fiber-driven stability, leading to reduced 3D cell body movement, metaphase plate rotations, increased interkinetochore distances, and significantly faster division times. Interestingly, interphase kite shapes on a crosshatch pattern of four fibers undergo mitosis resembling single-fiber outcomes due to rounded bodies being primarily held in position by RFs from two perpendicular suspended fibers. We develop a cortex-astral microtubule analytical model to capture the retraction fiber dependence of the metaphase plate rotations. We observe that reduced orientational stability, on single fibers, results in increased monopolar mitotic defects, while multipolar defects become dominant as the number of adhered fibers increases. We use a stochastic Monte Carlo simulation of centrosome, chromosome, and membrane interactions to explain the relationship between the observed propensity of monopolar and multipolar defects and the geometry of RFs. Overall, we establish that while bipolar mitosis is robust in fibrous environments, the nature of division errors in fibrous microenvironments is governed by interphase cell shapes and adhesion geometries.
    Keywords:  cell division; mitotic cell rounding; mitotic spindle; nanofibers; retraction fibers
    DOI:  https://doi.org/10.1073/pnas.2120536120
  2. Genes Dev. 2023 Mar 01.
    Adaptation to spindle assembly checkpoint inhibition through the selection of specific aneuploidies.
    Manuel Alonso Y Adell, Tamara C Klockner, Rudolf Höfler, Lea Wallner, Julia Schmid, Ana Markovic, Anastasiia Martyniak, Christopher S Campbell.
      Both the presence of an abnormal complement of chromosomes (aneuploidy) and an increased frequency of chromosome missegregation (chromosomal instability) are hallmarks of cancer. Analyses of cancer genome data have identified certain aneuploidy patterns in tumors; however, the bases behind their selection are largely unexplored. By establishing time-resolved long-term adaptation protocols, we found that human cells adapt to persistent spindle assembly checkpoint (SAC) inhibition by acquiring specific chromosome arm gains and losses. Independently adapted populations converge on complex karyotypes, which over time are refined to contain ever smaller chromosomal changes. Of note, the frequencies of chromosome arm gains in adapted cells correlate with those detected in cancers, suggesting that our cellular adaptation approach recapitulates selective traits that dictate the selection of aneuploidies frequently observed across many cancer types. We further engineered specific aneuploidies to determine the genetic basis behind the observed karyotype patterns. These experiments demonstrated that the adapted and engineered aneuploid cell lines limit CIN by extending mitotic duration. Heterozygous deletions of key SAC and APC/C genes recapitulated the rescue phenotypes of the monosomic chromosomes. We conclude that aneuploidy-induced gene dosage imbalances of individual mitotic regulators are sufficient for altering mitotic timing to reduce CIN.
    Keywords:  MPS1; aneuploidy patterns; chromosomal instability; drug resistance mechanisms; spindle assembly checkpoint
    DOI:  https://doi.org/10.1101/gad.350182.122
  3. J Cell Sci. 2023 Mar 01. pii: jcs220269. [Epub ahead of print]136(5):
    Dynein at the kinetochore.
    Reto Gassmann.
      The microtubule minus-end-directed motility of cytoplasmic dynein 1 (dynein), arguably the most complex and versatile cytoskeletal motor, is harnessed for diverse functions, such as long-range organelle transport in neuronal axons and spindle assembly in dividing cells. The versatility of dynein raises a number of intriguing questions, including how is dynein recruited to its diverse cargo, how is recruitment coupled to activation of the motor, how is motility regulated to meet different requirements for force production and how does dynein coordinate its activity with that of other microtubule-associated proteins (MAPs) present on the same cargo. Here, these questions will be discussed in the context of dynein at the kinetochore, the supramolecular protein structure that connects segregating chromosomes to spindle microtubules in dividing cells. As the first kinetochore-localized MAP described, dynein has intrigued cell biologists for more than three decades. The first part of this Review summarizes current knowledge about how kinetochore dynein contributes to efficient and accurate spindle assembly, and the second part describes the underlying molecular mechanisms and highlights emerging commonalities with dynein regulation at other subcellular sites.
    Keywords:  CENP-F; Corona; Dynein; Kinetochore; Lis1; Mitosis; Nde1; Ndel1; RZZ; Spindly
    DOI:  https://doi.org/10.1242/jcs.220269
  4. Stem Cell Rev Rep. 2023 Mar 02.
    TPX2 Amplification-Driven Aberrant Mitosis in Culture Adapted Human Embryonic Stem Cells with gain of 20q11.21.
    Ho-Chang Jeong, Young-Hyun Go, Joong-Gon Shin, Yun-Jeong Kim, Min-Guk Cho, Dasom Gwon, Hyun Sub Cheong, Haeseung Lee, Jae-Ho Lee, Chang-Young Jang, Hyoung Doo Shin, Hyuk-Jin Cha.
       BACKGROUND: Despite highly effective machinery for the maintenance of genome integrity in human embryonic stem cells (hESCs), the frequency of genetic aberrations during in-vitro culture has been a serious issue for future clinical applications.
    METHOD: By passaging hESCs over a broad range of timepoints (up to 6 years), the isogenic hESC lines with different passage numbers with distinct cellular characteristics, were established.
    RESULT: We found that mitotic aberrations, such as the delay of mitosis, multipolar centrosomes, and chromosome mis-segregation, were increased in parallel with polyploidy compared to early-passaged hESCs (EP-hESCs) with normal copy number. Through high-resolution genome-wide approaches and transcriptome analysis, we found that culture adapted-hESCs with a minimal amplicon in chromosome 20q11.21 highly expressed TPX2, a key protein for governing spindle assembly and cancer malignancy. Consistent with these findings, the inducible expression of TPX2 in EP-hESCs reproduced aberrant mitotic events, such as the delay of mitotic progression, spindle stabilization, misaligned chromosomes, and polyploidy.
    CONCLUSION: These studies suggest that the increased transcription of TPX2 in culture adapted hESCs could contribute to an increase in aberrant mitosis due to altered spindle dynamics.
    Keywords:  20q11.21 amplicon; Chromosome instability; Culture adaptation; Embryonic stem cells; TPX2
    DOI:  https://doi.org/10.1007/s12015-023-10514-4
  5. bioRxiv. 2023 Feb 22. pii: 2023.02.21.528438. [Epub ahead of print]
    Mechanisms of Nuclear Pore Complex disassembly by the mitotic Polo-Like Kinase 1 (PLK-1) in C. elegans embryos.
    Sylvia Nkombo Nkoula, Griselda Velez-Aguilera, Batool Ossareh-Nazari, Lucie Van Hove, Cristina Ayuso, Véronique Legros, Guillaume Chevreux, Laura Thomas, Géraldine Seydoux, Peter Askjaer, Lionel Pintard.
      The nuclear envelope, which protects and organizes the interphase genome, is dismantled during mitosis. In the C. elegans zygote, nuclear envelope breakdown (NEBD) of the parental pronuclei is spatially and temporally regulated during mitosis to promote the unification of the parental genomes. During NEBD, Nuclear Pore Complex (NPC) disassembly is critical for rupturing the nuclear permeability barrier and removing the NPCs from the membranes near the centrosomes and between the juxtaposed pronuclei. By combining live imaging, biochemistry, and phosphoproteomics, we characterized NPC disassembly and unveiled the exact role of the mitotic kinase PLK-1 in this process. We show that PLK-1 disassembles the NPC by targeting multiple NPC sub-complexes, including the cytoplasmic filaments, the central channel, and the inner ring. Notably, PLK-1 is recruited to and phosphorylates intrinsically disordered regions of several multivalent linker nucleoporins, a mechanism that appears to be an evolutionarily conserved driver of NPC disassembly during mitosis. (149/150 words).
    One-Sentence Summary: PLK-1 targets intrinsically disordered regions of multiple multivalent nucleoporins to dismantle the nuclear pore complexes in the C. elegans zygote.
    DOI:  https://doi.org/10.1101/2023.02.21.528438
  6. Cytogenet Genome Res. 2023 Mar 02. 162(6): 1-14
    Shugoshin Regulates Cohesin, Kinetochore-Microtubule Attachments, and Chromosomal Instability.
    Qiqi Sun, Feng Liu, Xiaolong Mo, Bo Yao, Guanghai Liu, Shanshan Chen, Yanping Ren.
      Correct regulation of cohesin at chromosome arms and centromeres and accurate kinetochore-microtubule connections are significant for proper chromosome segregation. At anaphase of meiosis I, cohesin at chromosome arms is cleaved by separase, leading to the separation of homologous chromosomes. However, at anaphase of meiosis II, cohesin at centromeres is cleaved by separase, leading to the separation of sister chromatids. Shugoshin-2 (SGO2) is a member of the shugoshin/MEI-S332 protein family in mammalian cells, a crucial protein that protects centromeric cohesin from cleavage by separase and corrects wrong kinetochore-microtubule connections before anaphase of meiosis I. Shugoshin-1 (SGO1) plays a similar role in mitosis. Moreover, shugoshin can inhibit the occurrence of chromosomal instability (CIN), and its abnormal expression in several tumors, such as triple-negative breast cancer, hepatocellular carcinoma, lung cancer, colon cancer, glioma, and acute myeloid leukemia, can be used as biomarker for disease progression and potential therapeutic targets for cancers. Thus, this review discusses the specific mechanisms of shugoshin which regulates cohesin, kinetochore-microtubule connections, and CIN.
    Keywords:  Chromosomal instability; Cohesin; Kinetochore-microtubule connection; Meiosis; Mitosis; Shugoshin
    DOI:  https://doi.org/10.1159/000528141
  7. J Microsc. 2023 Mar 02.
    The restriction of calcium influx in metaphase and post-metaphase stages of cell division revealed by imaging secondary ion mass spectrometry (SIMS).
    Subhash Chandra.
      A secondary ion mass spectrometry (SIMS) based isotopic imaging technique of ion microscopy was used for observing calcium influx in single renal epithelial LLC-PK1 cells. The CAMECA IMS-3f SIMS instrument, used in the study, is capable of producing isotopic images of single cells at 500 nm spatial resolution. Due to the high vacuum requirements of the instrument the cells were prepared cryogenically with a freeze-fracture method and frozen freeze-dried cells were used for SIMS analysis. The influx of calcium was imaged directly by exposure of cells to 44 Ca stable isotope in the extracellular buffer for 10 min. The 44 Ca influx was measured at mass 44 and the distribution of endogenous calcium at mass 40 (40 Ca) in the same cell. A direct comparison of interphase cells to cells undergoing division revealed that calcium influx is restricted in metaphase and post-metaphase stages of cell division. This restriction is lifted in late cytokinesis. The net influx of 44 Ca in 10 min. was approximately half under calcium influx restriction in comparison to interphase cells. Under calcium influx restriction the 44 Ca concentration was the same between the mitotic chromosome and the cytoplasm. These observations indicate that the endoplasmic reticulum (ER) calcium uptake is compromised under calcium influx restriction in cells undergoing division. This article is protected by copyright. All rights reserved.
    Keywords:  Calcium Signaling; Calcium and Mitosis; Calcium influx restriction in cell division; Calcium physiology; Secondary Ion Mass Spectrometry
    DOI:  https://doi.org/10.1111/jmi.13182
  8. Planta. 2023 Mar 02. 257(4): 71
    Rice kinesin-related protein STD1 and microtubule-associated protein MAP65-5 cooperatively control microtubule bundling.
    Jingjing Fang, Yan Chun, Tingting Guo, Mengmeng Ren, Jinfeng Zhao, Xueyong Li.
       MAIN CONCLUSIONS: STD1 specifically interacts with MAP65-5 in rice and they cooperatively control microtubule bundles in phragmoplast expansion during cell division. Microtubules play critical roles during the cell cycle progression in the plant cell. We previously reported that STEMLESS DWARF 1 (STD1), a kinesin-related protein, was localized specifically to the phragmoplast midzone during telophase to regulate the lateral expansion of phragmoplast in rice (Oryza sativa). However, how STD1 regulates microtubule organization remains unknown. Here, we found that STD1 interacted directly with MAP65-5, a member of the microtubule-associated proteins (MAPs). Both STD1 and MAP65-5 could form homodimers and bundle microtubules individually. Compared with MAP65-5, the microtubules bundled by STD1 were disassembled completely into single microtubules after adding ATP. Conversely, the interaction of STD1 with MAP65-5 enhanced the microtubule bundling. These results suggest STD1 and MAP65-5 might cooperatively regulate microtubule organization in the phragmoplast at telophase.
    Keywords:  Cell division; Kinesin; Microtubule bundling; Microtubule-associated proteins; Phragmoplast
    DOI:  https://doi.org/10.1007/s00425-023-04106-2
  9. Epilepsia. 2023 Mar 04.
    Cannabinoid regulation of neurons in the dentate gyrus during epileptogenesis. Role of CB1R-associated proteins and downstream pathways.
    Carlos A Lafourcade, Fraser T Sparks, Angelique Bordey, Ursula Wyneken, Michael H Mohammadi.
      The hippocampal formation plays a central role in the development of temporal lobe epilepsy (TLE), a disease characterized by recurrent, unprovoked epileptic discharges. TLE is a neurologic disorder characterized by acute long-lasting seizures (i.e. abnormal electrical activity in the brain) or seizures that occur in close proximity without recovery, typically after a brain injury or status epilepticus. After status epilepticus, epileptogenic hyperexcitability develops gradually over the following months to years resulting in the emergence of chronic, recurrent seizures. Acting as a filter or gate, the hippocampal dentate gyrus (DG) normally prevents excessive excitation from propagating through the hippocampus, and is considered a critical region in the progression of epileptogenesis in pathological conditions. Importantly, lipid-derived endogenous cannabinoids (endocannabinoids, eCBs), which are produced-on-demand as retrograde messengers, are central regulators of neuronal activity in the DG circuit (Sugaya et al., 2016). In this review, we summarize recent findings concerning the role of the DG in controlling hyperexcitability and propose how DG regulation by cannabinoids (CBs) could provide avenues for therapeutic interventions. We also highlight possible pathways and manipulations that could be relevant for the control of hyperexcitation.
    DOI:  https://doi.org/10.1111/epi.17569
This page is being maintained by Thomas Krichel. It was last updated on 2024‒11‒22 at 4:21.