1. Cell Biology
  2. Computational and Systems Biology
Download icon

The nucleus serves as the pacemaker for the cell cycle

  1. Oshri Afanzar
  2. Garrison K Buss
  3. Tim Stearns
  4. James E Ferrell Jr.  Is a corresponding author
  1. Stanford Medicine, United States
  2. Stanford University, United States
Research Article
  • Cited 7
  • Views 3,146
  • Annotations
Cite this article as: eLife 2020;9:e59989 doi: 10.7554/eLife.59989

Abstract

Mitosis is a dramatic process that affects all parts of the cell. It is driven by an oscillator whose various components are localized in the nucleus, centrosome, and cytoplasm. In principle, the cellular location with the fastest intrinsic rhythm should act as a pacemaker for the process. Here we traced the waves of tubulin polymerization and depolymerization that occur at mitotic entry and exit in Xenopus egg extracts back to their origins. We found that mitosis was commonly initiated at sperm-derived nuclei and their accompanying centrosomes. The cell cycle was ~20% faster at these initiation points than in the slowest regions of the extract. Nuclei produced from phage DNA, which did not possess centrosomes, also acted as trigger wave sources, but purified centrosomes in the absence of nuclei did not. We conclude that the nucleus accelerates mitotic entry and propose that it acts as a pacemaker for cell cycle.

Data availability

All data and code used in the analysis are available from the Stanford Digital Repository (https://purl.stanford.edu/fm814ch0699) for purposes of reproducing or extending the analysis.

The following data sets were generated

Article and author information

Author details

  1. Oshri Afanzar

    Chemical and Systems Biology, Stanford Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Garrison K Buss

    Molecular and Cellular Physiology, Stanford Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Tim Stearns

    Department of Biology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0671-6582
  4. James E Ferrell Jr.

    Department of Chemical and Systems Biology and Department of Biochemistry, Stanford Medicine, Stanford, United States
    For correspondence
    james.ferrell@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4767-3926

Funding

National Institutes of Health (R01 GM110564)

  • James E Ferrell Jr.

National Institutes of Health (R35 GM131792)

  • James E Ferrell Jr.

National Institutes of Health (R35 GM120286)

  • Tim Stearns

National Institutes of Health (GM007276)

  • Garrison K Buss

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols Stanford University (assurance no. A3213-01, protocol 13307).

Reviewing Editor

  1. Stefano Di Talia, Duke University, United States

Publication history

  1. Received: June 15, 2020
  2. Accepted: December 6, 2020
  3. Accepted Manuscript published: December 7, 2020 (version 1)
  4. Version of Record published: December 22, 2020 (version 2)
  5. Version of Record updated: December 23, 2020 (version 3)

Copyright

© 2020, Afanzar 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

  • 3,146
    Page views
  • 284
    Downloads
  • 7
    Citations

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. Developmental Biology
    Elise Houssin et al.
    Research Article Updated

    In multiple cell lineages, Delta-Notch signalling regulates cell fate decisions owing to unidirectional signalling between daughter cells. In Drosophila pupal sensory organ lineage, Notch regulates the intra-lineage pIIa/pIIb fate decision at cytokinesis. Notch and Delta that localise apically and basally at the pIIa-pIIb interface are expressed at low levels and their residence time at the plasma membrane is in the order of minutes. How Delta can effectively interact with Notch to trigger signalling from a large plasma membrane area remains poorly understood. Here, we report that the signalling interface possesses a unique apico-basal polarity with Par3/Bazooka localising in the form of nano-clusters at the apical and basal level. Notch is preferentially targeted to the pIIa-pIIb interface, where it co-clusters with Bazooka and its cofactor Sanpodo. Clusters whose assembly relies on Bazooka and Sanpodo activities are also positive for Neuralized, the E3 ligase required for Delta activity. We propose that the nano-clusters act as snap buttons at the new pIIa-pIIb interface to allow efficient intra-lineage signalling.

    1. Cell Biology
    2. Neuroscience
    Zhong-Jiao Jiang et al.
    Research Article Updated

    Transient receptor potential melastatin 7 (TRPM7) contributes to a variety of physiological and pathological processes in many tissues and cells. With a widespread distribution in the nervous system, TRPM7 is involved in animal behaviors and neuronal death induced by ischemia. However, the physiological role of TRPM7 in central nervous system (CNS) neuron remains unclear. Here, we identify endocytic defects in neuroendocrine cells and neurons from TRPM7 knockout (KO) mice, indicating a role of TRPM7 in synaptic vesicle endocytosis. Our experiments further pinpoint the importance of TRPM7 as an ion channel in synaptic vesicle endocytosis. Ca2+ imaging detects a defect in presynaptic Ca2+ dynamics in TRPM7 KO neuron, suggesting an importance of Ca2+ influx via TRPM7 in synaptic vesicle endocytosis. Moreover, the short-term depression is enhanced in both excitatory and inhibitory synaptic transmissions from TRPM7 KO mice. Taken together, our data suggests that Ca2+ influx via TRPM7 may be critical for short-term plasticity of synaptic strength by regulating synaptic vesicle endocytosis in neurons.