Polo-like kinase acts as a molecular timer that safeguards the asymmetric fate of spindle microtubule-organizing centers

  1. Laura Matellán
  2. Javier Manzano-López
  3. Fernando Monje-Casas  Is a corresponding author
  1. University of Seville, Spain
  2. Spanish National Research Council (CSIC), Spain

Abstract

The microtubules that form the mitotic spindle originate from microtubule organizing centers (MTOCs) located at either pole. After duplication, spindle MTOCs can be differentially inherited during asymmetric cell division in organisms ranging from yeast to humans. Problems with establishing predetermined spindle MTOC inheritance patterns during stem cell division have been associated with accelerated cellular aging and the development of both cancer and neurodegenerative disorders. Here, we expand the repertoire of functions Polo-like kinase family members fulfill in regulating pivotal cell cycle processes. We demonstrate that the Plk1 homolog Cdc5 acts as a molecular timer that facilitates the timely and sequential recruitment of two key determinants of spindle MTOCs distribution, i.e., the γ-tubulin complex receptor Spc72 and the protein Kar9, and establishes the fate of these structures, safeguarding their asymmetric inheritance during Saccharomyces cerevisiae mitosis.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. No new datasets were generated or previously published datasets used in our work. Rich media files such as videos, audio clips or animations were also not created for this article. No further relevant additional data file was provided.

Article and author information

Author details

  1. Laura Matellán

    CABIMER, University of Seville, Seville, Spain
    Competing interests
    The authors declare that no competing interests exist.
  2. Javier Manzano-López

    CABIMER, Spanish National Research Council (CSIC), Seville, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Fernando Monje-Casas

    CABIMER, Spanish National Research Council (CSIC), Seville, Spain
    For correspondence
    fernando.monje@cabimer.es
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3587-2373

Funding

Spanish Ministry of Economy, Industry and Competitiveness and European Union (BFU2013-43718-P)

  • Fernando Monje-Casas

Spanish Ministry of Economy, Industry and Competitiveness and European Union (BFU2016-76642-P)

  • Fernando Monje-Casas

Spanish Ministry of Economy, Industry and Competitiveness and European Union (FPI fellowship)

  • Laura Matellán

Spanish Ministry of Economy, Industry and Competitiveness and European Union (Juan de la Cierva research contract)

  • Javier Manzano-López

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2020, Matellán et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,579
    views
  • 281
    downloads
  • 4
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Laura Matellán
  2. Javier Manzano-López
  3. Fernando Monje-Casas
(2020)
Polo-like kinase acts as a molecular timer that safeguards the asymmetric fate of spindle microtubule-organizing centers
eLife 9:e61488.
https://doi.org/10.7554/eLife.61488

Share this article

https://doi.org/10.7554/eLife.61488

Further reading

    1. Cell Biology
    2. Neuroscience
    Naoki Yamawaki, Hande Login ... Asami Tanimura
    Research Article

    The claustrum complex is viewed as fundamental for higher-order cognition; however, the circuit organization and function of its neuroanatomical subregions are not well understood. We demonstrated that some of the key roles of the CLA complex can be attributed to the connectivity and function of a small group of neurons in its ventral subregion, the endopiriform (EN). We identified a subpopulation of EN neurons by their projection to the ventral CA1 (ENvCA1-proj. neurons), embedded in recurrent circuits with other EN neurons and the piriform cortex. Although the ENvCA1-proj. neuron activity was biased toward novelty across stimulus categories, their chemogenetic inhibition selectively disrupted the memory-guided but not innate responses of mice to novelty. Based on our functional connectivity analysis, we suggest that ENvCA1-proj. neurons serve as an essential node for recognition memory through recurrent circuits mediating sustained attention to novelty, and through feed-forward inhibition of distal vCA1 neurons shifting memory-guided behavior from familiarity to novelty.

    1. Cell Biology
    2. Computational and Systems Biology
    Sarah De Beuckeleer, Tim Van De Looverbosch ... Winnok H De Vos
    Research Article

    Induced pluripotent stem cell (iPSC) technology is revolutionizing cell biology. However, the variability between individual iPSC lines and the lack of efficient technology to comprehensively characterize iPSC-derived cell types hinder its adoption in routine preclinical screening settings. To facilitate the validation of iPSC-derived cell culture composition, we have implemented an imaging assay based on cell painting and convolutional neural networks to recognize cell types in dense and mixed cultures with high fidelity. We have benchmarked our approach using pure and mixed cultures of neuroblastoma and astrocytoma cell lines and attained a classification accuracy above 96%. Through iterative data erosion, we found that inputs containing the nuclear region of interest and its close environment, allow achieving equally high classification accuracy as inputs containing the whole cell for semi-confluent cultures and preserved prediction accuracy even in very dense cultures. We then applied this regionally restricted cell profiling approach to evaluate the differentiation status of iPSC-derived neural cultures, by determining the ratio of postmitotic neurons and neural progenitors. We found that the cell-based prediction significantly outperformed an approach in which the population-level time in culture was used as a classification criterion (96% vs 86%, respectively). In mixed iPSC-derived neuronal cultures, microglia could be unequivocally discriminated from neurons, regardless of their reactivity state, and a tiered strategy allowed for further distinguishing activated from non-activated cell states, albeit with lower accuracy. Thus, morphological single-cell profiling provides a means to quantify cell composition in complex mixed neural cultures and holds promise for use in the quality control of iPSC-derived cell culture models.