The step-wise pathway of septin hetero-octamer assembly in budding yeast

  1. Andrew D Weems
  2. Michael A McMurray  Is a corresponding author
  1. University of Colorado Anschutz Medical Campus, United States

Abstract

Septin proteins bind guanine nucleotides and form rod-shaped hetero-oligomers. Cells choose from a variety of available septins to assemble distinct hetero-oligomers, but the underlying mechanism was unknown. Using a new in vivo assay, we find that a stepwise assembly pathway produces the two species of budding yeast septin hetero-octamers: Cdc11/Shs1–Cdc12–Cdc3–Cdc10–Cdc10–Cdc3–Cdc12–Cdc11/Shs1. Rapid GTP hydrolysis by monomeric Cdc10 drives assembly of the core Cdc10 homodimer. The extended Cdc3 N terminus autoinhibits Cdc3 association with Cdc10 homodimers until prior Cdc3–Cdc12 interaction. Slow hydrolysis by monomeric Cdc12 and specific affinity of Cdc11 for transient Cdc12•GTP drive assembly of distinct trimers, Cdc11–Cdc12–Cdc3 or Shs1–Cdc12–Cdc3. Decreasing the cytosolic GTP:GDP ratio increases the incorporation of Shs1 vs Cdc11, which alters the curvature of filamentous septin rings. Our findings explain how GTP hydrolysis controls septin assembly, and uncover mechanisms by which cells construct defined septin complexes.

Article and author information

Author details

  1. 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.
  2. Michael A McMurray

    Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
    For correspondence
    michael.mcmurray@ucdenver.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

Alzheimer's Association (NIRGD-12-241119)

  • Michael A McMurray

National Institute of General Medical Sciences (R00GM086603)

  • Michael A McMurray

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

Reviewing Editor

  1. Yves Barral, Eidgenössische Technische Hochschule Zürich, Switzerland

Version history

  1. Received: January 2, 2017
  2. Accepted: May 24, 2017
  3. Accepted Manuscript published: May 25, 2017 (version 1)
  4. Version of Record published: June 6, 2017 (version 2)

Copyright

© 2017, Weems & McMurray

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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  1. Andrew D Weems
  2. Michael A McMurray
(2017)
The step-wise pathway of septin hetero-octamer assembly in budding yeast
eLife 6:e23689.
https://doi.org/10.7554/eLife.23689

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https://doi.org/10.7554/eLife.23689

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