Kinesin Kip2 enhances microtubule growth in vitro through length-dependent feedback on polymerization and catastrophe

  1. Anneke Hibbel
  2. Aliona Bogdanova
  3. Mohammed Mahamdeh
  4. Anita Jannasch
  5. Marko Storch
  6. Erik Schäffer
  7. Dimitris Liakopoulos
  8. Jonathon Howard  Is a corresponding author
  1. Max Planck Institute of Molecular Cell Biology and Genetics, Germany
  2. Yale University, United States
  3. Imperial College London, United Kingdom
  4. Eberhard-Karls-Universität Tübingen, Germany
  5. Centre de Recherche de Biochimie Macromoléculaire, France

Abstract

The size and position of mitotic spindles is determined by the lengths of their constituent microtubules. Regulation of microtubule length requires feedback to set the balance between growth and shrinkage. Whereas negative feedback mechanisms for microtubule length control, based on depolymerizing kinesins and severing proteins, have been studied extensively, positive feedback mechanisms are not known. Here we report that the budding yeast kinesin Kip2 is a microtubule polymerase and catastrophe inhibitor in vitro that uses its processive motor activity as part of a feedback loop to further promote microtubule growth. Positive feedback arises because longer microtubules bind more motors, which walk to the ends where they further reinforce growth and inhibit catastrophe. We propose that positive feedback, common in biochemical pathways to switch between signaling states, can also be used in a mechanical signaling pathway to switch between structural states, in this case between short and long polymers.

Article and author information

Author details

  1. Anneke Hibbel

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Aliona Bogdanova

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Mohammed Mahamdeh

    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Anita Jannasch

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Marko Storch

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Erik Schäffer

    Zentrum für Molekularbiologie der Pflanzen, Eberhard-Karls-Universität Tübingen, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Dimitris Liakopoulos

    Centre de Recherche de Biochimie Macromoléculaire, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Jonathon Howard

    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States
    For correspondence
    jonathon.howard@yale.edu
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2015, Hibbel 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

  • 2,954
    views
  • 734
    downloads
  • 45
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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)

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

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

  1. Anneke Hibbel
  2. Aliona Bogdanova
  3. Mohammed Mahamdeh
  4. Anita Jannasch
  5. Marko Storch
  6. Erik Schäffer
  7. Dimitris Liakopoulos
  8. Jonathon Howard
(2015)
Kinesin Kip2 enhances microtubule growth in vitro through length-dependent feedback on polymerization and catastrophe
eLife 4:e10542.
https://doi.org/10.7554/eLife.10542

Share this article

https://doi.org/10.7554/eLife.10542

Further reading

    1. Structural Biology and Molecular Biophysics
    Laura-Marie Silbermann, Benjamin Vermeer ... Katarzyna Tych
    Review Article

    Molecular chaperones are vital proteins that maintain protein homeostasis by assisting in protein folding, activation, degradation, and stress protection. Among them, heat-shock protein 90 (Hsp90) stands out as an essential proteostasis hub in eukaryotes, chaperoning hundreds of ‘clients’ (substrates). After decades of research, several ‘known unknowns’ about the molecular function of Hsp90 remain unanswered, hampering rational drug design for the treatment of cancers, neurodegenerative, and other diseases. We highlight three fundamental open questions, reviewing the current state of the field for each, and discuss new opportunities, including single-molecule technologies, to answer the known unknowns of the Hsp90 chaperone.

    1. Structural Biology and Molecular Biophysics
    Chuchu Wang, Chunyu Zhao ... Cong Liu
    Research Advance

    Previously, we reported that α-synuclein (α-syn) clusters synaptic vesicles (SV) Diao et al., 2013, and neutral phospholipid lysophosphatidylcholine (LPC) can mediate this clustering Lai et al., 2023. Meanwhile, post-translational modifications (PTMs) of α-syn such as acetylation and phosphorylation play important yet distinct roles in regulating α-syn conformation, membrane binding, and amyloid aggregation. However, how PTMs regulate α-syn function in presynaptic terminals remains unclear. Here, based on our previous findings, we further demonstrate that N-terminal acetylation, which occurs under physiological conditions and is irreversible in mammalian cells, significantly enhances the functional activity of α-syn in clustering SVs. Mechanistic studies reveal that this enhancement is caused by the N-acetylation-promoted insertion of α-syn’s N-terminus and increased intermolecular interactions on the LPC-containing membrane. N-acetylation in our work is shown to fine-tune the interaction between α-syn and LPC, mediating α-syn’s role in synaptic vesicle clustering.