1. Cell Biology
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The Mitotic Exit Network integrates temporal and spatial signals by distributing regulation across multiple components

  1. Ian Winsten Campbell
  2. Xiaoxue Zhou
  3. Angelika Amon  Is a corresponding author
  1. Howard Hughes Medical Institute, Massachusetts Institute of Technology, United States
Research Article
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Cite this article as: eLife 2019;8:e41139 doi: 10.7554/eLife.41139

Abstract

GTPase signal transduction pathways control cellular decision making by integrating multiple cellular events into a single signal. The Mitotic Exit Network (MEN), a Ras-like GTPase signaling pathway, integrates spatial and temporal cues to ensure that cytokinesis only occurs after the genome has partitioned between mother and daughter cells during anaphase. Here we show that signal integration does not occur at a single step of the pathway. Rather, sequential components of the pathway are controlled in series by different signals. The spatial signal, nuclear position, regulates the MEN GTPase Tem1. The temporal signal, commencement of anaphase, is mediated by mitotic cyclin-dependent kinase (CDK) phosphorylation of the GTPase's downstream kinases. We propose that integrating multiple signals through sequential steps in the GTPase pathway represents a generalizable principle in GTPase signaling and explains why intracellular signal transmission is a multi-step process. Serial signal integration rather than signal amplification makes multi-step signal transduction necessary.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Ian Winsten Campbell

    David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Xiaoxue Zhou

    David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Angelika Amon

    David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United States
    For correspondence
    angelika@mit.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9837-0314

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD085866)

  • Angelika Amon

Howard Hughes Medical Institute

  • Angelika Amon

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

Reviewing Editor

  1. Jon Pines, Institute of Cancer Research Research, United Kingdom

Publication history

  1. Received: August 15, 2018
  2. Accepted: January 10, 2019
  3. Accepted Manuscript published: January 23, 2019 (version 1)
  4. Version of Record published: February 5, 2019 (version 2)

Copyright

© 2019, Campbell 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.

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