1. Biochemistry and Chemical Biology
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Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast

  1. Courtney R Johnson
  2. Marc G Steingesser
  3. Andrew D Weems
  4. Anum Khan
  5. Amy Galdfelter
  6. Aurélie Bertin
  7. Michael A McMurray  Is a corresponding author
  1. University of Colorado Anschutz Medical Campus, United States
  2. University of North Carolina at Chapel Hill, United States
  3. Institut Curie, France
Research Article
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Cite this article as: eLife 2020;9:e54355 doi: 10.7554/eLife.54355

Abstract

Septin proteins evolved from ancestral GTPases and co-assemble into hetero-oligomers and cytoskeletal filaments. In Saccharomyces cerevisiae, five septins comprise two species of hetero-octamers, Cdc11/Shs1–Cdc12–Cdc3–Cdc10–Cdc10–Cdc3–Cdc12–Cdc11/Shs1. Slow GTPase activity by Cdc12 directs the choice of incorporation of Cdc11 vs Shs1, but many septins, including Cdc3, lack GTPase activity. We serendipitously discovered that guanidine hydrochloride rescues septin function in cdc10 mutants by promoting assembly of non-native Cdc11/Shs1–Cdc12–Cdc3–Cdc3–Cdc12–Cdc11/Shs1 hexamers. We provide evidence that in S. cerevisiae Cdc3 guanidinium occupies the site of a 'missing' Arg side chain found in other fungal species where (i) the Cdc3 subunit is an active GTPase and (ii) Cdc10-less hexamers natively co-exist with octamers. We propose that guanidinium reactivates a latent septin assembly pathway that was suppressed during fungal evolution in order to restrict assembly to octamers. Since homodimerization by a GTPase-active human septin also creates hexamers that exclude Cdc10-like central subunits, our new mechanistic insights likely apply throughout phylogeny.

Article and author information

Author details

  1. Courtney R Johnson

    Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Marc G Steingesser

    Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Andrew D Weems

    Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Anum Khan

    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Amy Galdfelter

    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Aurélie Bertin

    Laboratoire Physico Chimie Curie, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Michael A McMurray

    Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
    For correspondence
    michael.mcmurray@cuanschutz.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4615-4334

Funding

National Institute of General Medical Sciences (R00GM086603)

  • Michael A McMurray

National Institute of General Medical Sciences (R01GM124024)

  • Michael A McMurray

Alzheimer's Association (NIRGD-12-241119)

  • Michael A McMurray

Rare Genomics Institute (BeHEARD Initiative)

  • Michael A McMurray

Agence Nationale de la Recherche (ANR-10-INSB-04)

  • Aurélie Bertin

Agence Nationale de la Recherche (ANR-10-LBX-0038)

  • Aurélie Bertin

National Science Foundation (MCB-1615138)

  • Anum Khan
  • Amy Galdfelter

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

Reviewing Editor

  1. Anna Akhmanova, Utrecht University, Netherlands

Publication history

  1. Received: December 11, 2019
  2. Accepted: January 25, 2020
  3. Accepted Manuscript published: January 28, 2020 (version 1)

Copyright

© 2020, Johnson 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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