Menu

Close

Lattice defects induce microtubule self-renewal

Laura Schaedel, Denis Chrétien, Charlotte Aumeier, Jérémie Gaillard, Laurent Blanchoin, Manuel Théry, Karin John

Preprint posted on January 16, 2018 https://www.biorxiv.org/content/early/2018/01/16/249144

How do microtubules repair themselves? Recent preprint shows the occurrence of tubulin dimer exchange all along the microtubules at sites of structural defects. After all, defects are a good thing!

Selected by Satish Bodakuntla

 

Context: The well-established microtubule property of dynamic instability allows them to co-exist in both growing and shrinking states. Nevertheless, the site of incorporation of tubulin dimers – laterally, or at the plus ends of microtubules – has long been discussed in the field. Latest studies showed that microtubules subjected to mechanical stress are able to self-repair by incorporating tubulin dimers laterally at the damaged sites.

Key findings: The authors investigate the possibility of spontaneous (in the absence of mechanical stress) microtubule turnover in vitro and provide insights on various factors that could influence this process. They discover the following:

  1. Tubulin incorporation occurs all along the microtubule shafts spontaneously and is dependent on the concentration of free tubulin, similar to what has been found at microtubule plus ends.
  2. Simulations of microtubule dynamics at the dislocation defects (changes in number of protofilaments and/or start number of helices) revealed that small lattice defects are sufficient to trigger tubulin dimer exchange.
  3. Increased free tubulin concentration enhances the microtubule growth rate, which in turn leads to higher lattice-defect frequencies.
  4. Higher lattice-defect frequencies are coupled with increased tubulin incorporation along the microtubule shafts.

Why I am interested in this preprint: Earlier studies from the authors showed that microtubules self-repair in response to mechanical stress, and provided very valuable insights in understanding how long-lived microtubules, such those in axons, tolerate forces they experience. Although there are reports supporting the entry of tubulin dimers along the microtubule shafts, the underlying mechanisms remained unexplored. In this preprint, the authors suggest a possible mechanism: structural defects, in particular, changes in protofilament number along microtubules can trigger the tubulin dimer exchange. Their experiments convincingly support the hypothesis.

In the light of their findings, it prompts us to rethink about the regulation of the microtubule cytoskeleton. Given the incorporation of tubulin dimers along the microtubule lattice, it is possible that this conformation of tubulin can recruit different microtubule-associated proteins thereby inducing dynamic changes in the microtubule properties. I believe the physiological implications of these phenomena will raise new challenging questions in the field.

Questions the work raises:

Microtubules in these experiments are prepared from purified brain tubulin, which is highly enriched with post-translational modifications. I would be curious to know how the results might change if authors had used non-modified tubulin.

 

Tags: dislocation defects, dynamic instability, lattice defects, microtubules

Posted on: 15th February 2018 , updated on: 20th February 2018

Read preprint (4 votes)




  • Author's response

    Manuel Thery shared

    The beauty of Laura’s work is that her minimalist approach, in which there is nothing else than tubulin in a very controled fluidic environment, allowed her to reveal a core microtubule property, which had remained hidden for many years behind many other effects that are inherent to more physiological but also more complex conditions.

    What she revealed is that microtubules are like us: they permanently self-renew. This observation demonstrates a mechanism that we had hypothesized in our previous study: the possibility to add or remove dimers in the lattice confers to microtubules the ability to self-repair in response to physical injuries. We are amazed by the level of plasticity in these structures! Furthermore, Laura showed, with the help of unpublished 25-year-old cryoEM experiments performed by Denis Chrétien, that renewal happens where tubulins lack one or two neighbours. I am quite excited by the idea that this could not happen in a perfect structure, at least in a reasonable amount of time. Defects make microtubules more sensitive, capable to adapt to external stimulations and probably to live longer.

    I found fascinating that this property to undergo permanent self-renewal without apparent changes, which is a characteristic of all living organisms, is so deeply buried in ourselves that it exist even in the filaments our cells are made of.

    Have your say

    Your email address will not be published. Required fields are marked *

    This site uses Akismet to reduce spam. Learn how your comment data is processed.

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the bioinformatics category:

    Lineage tracing on transcriptional landscapes links state to fate during differentiation

    Caleb Weinreb, Alejo E Rodriguez-Fraticelli, Fernando D Camargo, et al.



    Selected by Yen-Chung Chen

    1

    Charting a tissue from single-cell transcriptomes

    Mor Nitzan, Nikos Karaiskos, Nir Friedman, et al.



    Selected by Irepan Salvador-Martinez

    Large-scale analyses of human microbiomes reveal thousands of small, novel genes and their predicted functions

    Hila Sberro, Nicholas Greenfield, Georgios Pavlopoulos, et al.



    Selected by Ganesh Kadamur

    Atlas of Subcellular RNA Localization Revealed by APEX-seq

    Furqan M Fazal, Shuo Han, Pornchai Kaewsapsak, et al.

    AND

    Proximity RNA labeling by APEX-Seq Reveals the Organization of Translation Initiation Complexes and Repressive RNA Granules

    Alejandro Padron, Shintaro Iwasaki, Nicholas Ingolia



    Selected by Christian Bates

    Applications, Promises, and Pitfalls of Deep Learning for Fluorescence Image Reconstruction

    Chinmay Belthangady , Loic A. Royer



    Selected by Romain F. Laine

    The embryonic transcriptome of Arabidopsis thaliana

    Falko Hofmann, Michael A Schon, Michael D Nodine



    Selected by Chandra Shekhar Misra

    1

    The landscape of antigen-specific T cells in human cancers

    Bo Li, Longchao Liu, Jian Zhang, et al.



    Selected by Rob Hynds

    1

    Single-cell RNA sequencing reveals novel cell differentiation dynamics during human airway epithelium regeneration

    Sandra Ruiz Garcia, Marie Deprez, Kevin Lebrigand, et al.



    Selected by Rob Hynds

    1

    PUMILIO hyperactivity drives premature aging of Norad-deficient mice

    Florian Kopp, Mehmet Yalvac, Beibei Chen, et al.



    Selected by Carmen Adriaens

    Target-specific precision of CRISPR-mediated genome editing

    Anob M Chakrabarti, Tristan Henser-Brownhill, Josep Monserrat, et al.



    Selected by Rob Hynds

    1

    Precise tuning of gene expression output levels in mammalian cells

    Yale S. Michaels, Mike B Barnkob, Hector Barbosa, et al.



    Selected by Tim Fessenden

    1

    Template switching causes artificial junction formation and false identification of circular RNAs

    Chong Tang, Tian Yu, Yeming Xie, et al.



    Selected by Fabio Liberante

    An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics

    Ilias Angelidis, Lukas M Simon, Isis E Fernandez, et al.



    Selected by Rob Hynds

    1

    SWI/SNF remains localized to chromatin in the presence of SCHLAP1

    Jesse R Raab, Keriayn N Smith, Camarie C Spear, et al.



    Selected by Carmen Adriaens

    1

    Atomic model of microtubule-bound tau

    Elizabeth H Kellogg, Nisreen M.A. Hejab, Simon Poepsel, et al.



    Selected by Satish Bodakuntla

    1

    Higher-Order Organization Principles of Pre-translational mRNPs

    Mihir Metkar, Hakan Ozadam, Bryan R. Lajoie, et al.



    Selected by Carmen Adriaens

    Also in the cell biology category:

    A DNA-based voltmeter for organelles

    Anand Saminathan, John Devany, Kavya S Pillai, et al.



    Selected by Robert Mahen

    Central spindle microtubules are strongly coupled to chromosomes during both anaphase A and anaphase B

    Che-Hang Yu, Stefanie Redemann, Hai-Yin Wu, et al.



    Selected by Federico Pelisch

    1

    Cell growth dilutes the cell cycle inhibitor Rb to trigger cell division

    Evgeny Zatulovskiy, Daniel F. Berenson, Benjamin R. Topacio, et al.



    Selected by Zaki Ahmad

    1

    Minimal membrane interactions conferred by Rheb C-terminal farnesylation are essential for mTORC1 activation

    Shawn M Ferguson, Brittany Angarola



    Selected by Sandra Malmgren Hill

    Mechanical Stretch Kills Transformed Cancer Cells

    Ajay Tijore, Mingxi Yao, Yu-Hsiu Wang, et al.



    Selected by Vibha SINGH

    EHD2-mediated restriction of caveolar dynamics regulates cellular lipid uptake

    Claudia Matthaeus, Ines Lahmann, Severine Kunz, et al.



    Selected by Andreas Müller

    1

    Mechanical Stretch Kills Transformed Cancer Cells

    Ajay Tijore, Mingxi Yao, Yu-Hsiu Wang, et al.



    Selected by Joseph Jose Thottacherry

    Inactive USP14 and inactive UCHL5 cause accumulation of distinct ubiquitinated proteins in mammalian cells

    Jayashree Chadchankar, Victoria Korboukh, Peter Doig, et al.



    Selected by Mila Basic

    A metabolic switch from OXPHOS to glycolysis is essential for cardiomyocyte proliferation in the regenerating heart

    Hessel Honkoop, Dennis de Bakker, Alla Aharonov, et al.



    Selected by Andreas van Impel

    1

    S-acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate desmosome assembly and cell adhesion.

    Keith T Woodley, Mark O Collins



    Selected by Abagael Lasseigne

    3

    A complex containing lysine-acetylated actin inhibits the formin INF2

    Mu A, Tak Shun Fung, Arminja N. Kettenbach, et al.



    Selected by Laura McCormick

    1

    Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells

    Quynh Nguyen, Zhen Liu, Rashmi Nanjundappa, et al.



    Selected by Robert Mahen

    Single cell RNA-Seq reveals distinct stem cell populations that drive sensory hair cell regeneration in response to loss of Fgf and Notch signaling

    Mark E. Lush, Daniel C. Diaz, Nina Koenecke, et al.

    AND

    Distinct progenitor populations mediate regeneration in the zebrafish lateral line.

    Eric D Thomas, David Raible



    Selected by Rudra Nayan Das

    1

    Actomyosin-II facilitates long-range retrograde transport of large cargoes by controlling axonal radial contractility

    Tong Wang, Wei Li, Sally Martin, et al.



    Selected by Ivana Viktorinová

    Atlas of Subcellular RNA Localization Revealed by APEX-seq

    Furqan M Fazal, Shuo Han, Pornchai Kaewsapsak, et al.

    AND

    Proximity RNA labeling by APEX-Seq Reveals the Organization of Translation Initiation Complexes and Repressive RNA Granules

    Alejandro Padron, Shintaro Iwasaki, Nicholas Ingolia



    Selected by Christian Bates

    Applications, Promises, and Pitfalls of Deep Learning for Fluorescence Image Reconstruction

    Chinmay Belthangady , Loic A. Royer



    Selected by Romain F. Laine
    Close