1. Cell Biology
Download icon

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
Research Article
  • Cited 0
  • Views 1,193
  • Annotations
Cite this article as: eLife 2020;9:e61488 doi: 10.7554/eLife.61488


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
    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


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.

Reviewing Editor

  1. Elçin Ünal, University of California, Berkeley, United States

Publication history

  1. Received: July 28, 2020
  2. Accepted: October 20, 2020
  3. Accepted Manuscript published: November 2, 2020 (version 1)
  4. Version of Record published: November 16, 2020 (version 2)


© 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.


  • 1,193
    Page views
  • 213
  • 0

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

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

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

Further reading

    1. Cell Biology
    2. Neuroscience
    Rene Solano Fonseca et al.
    Research Article Updated

    Concussion is associated with a myriad of deleterious immediate and long-term consequences. Yet the molecular mechanisms and genetic targets promoting the selective vulnerability of different neural subtypes to dysfunction and degeneration remain unclear. Translating experimental models of blunt force trauma in C. elegans to concussion in mice, we identify a conserved neuroprotective mechanism in which reduction of mitochondrial electron flux through complex IV suppresses trauma-induced degeneration of the highly vulnerable dopaminergic neurons. Reducing cytochrome C oxidase function elevates mitochondrial-derived reactive oxygen species, which signal through the cytosolic hypoxia inducing transcription factor, Hif1a, to promote hyperphosphorylation and inactivation of the pyruvate dehydrogenase, PDHE1α. This critical enzyme initiates the Warburg shunt, which drives energetic reallocation from mitochondrial respiration to astrocyte-mediated glycolysis in a neuroprotective manner. These studies demonstrate a conserved process in which glycolytic preconditioning suppresses Parkinson-like hypersensitivity of dopaminergic neurons to trauma-induced degeneration via redox signaling and the Warburg effect.

    1. Biochemistry and Chemical Biology
    2. Cell Biology
    Zdravka Daneva et al.
    Research Article Updated

    Pannexin 1 (Panx1), an ATP-efflux pathway, has been linked with inflammation in pulmonary capillaries. However, the physiological roles of endothelial Panx1 in the pulmonary vasculature are unknown. Endothelial transient receptor potential vanilloid 4 (TRPV4) channels lower pulmonary artery (PA) contractility and exogenous ATP activates endothelial TRPV4 channels. We hypothesized that endothelial Panx1–ATP–TRPV4 channel signaling promotes vasodilation and lowers pulmonary arterial pressure (PAP). Endothelial, but not smooth muscle, knockout of Panx1 increased PA contractility and raised PAP in mice. Flow/shear stress increased ATP efflux through endothelial Panx1 in PAs. Panx1-effluxed extracellular ATP signaled through purinergic P2Y2 receptor (P2Y2R) to activate protein kinase Cα (PKCα), which in turn activated endothelial TRPV4 channels. Finally, caveolin-1 provided a signaling scaffold for endothelial Panx1, P2Y2R, PKCα, and TRPV4 channels in PAs, promoting their spatial proximity and enabling signaling interactions. These results indicate that endothelial Panx1–P2Y2R–TRPV4 channel signaling, facilitated by caveolin-1, reduces PA contractility and lowers PAP in mice.