IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39646-4.html
   My bibliography  Save this article

Allosteric activation of vinculin by talin

Author

Listed:
  • Florian Franz

    (Heidelberg Institute for Theoretical Studies (HITS)
    Heidelberg University, Mathematikon, INF 205)

  • Rafael Tapia-Rojo

    (King’s College London
    The Francis Crick Institute)

  • Sabina Winograd-Katz

    (Weizmann Institute of Science)

  • Rajaa Boujemaa-Paterski

    (University of Zurich)

  • Wenhong Li

    (Weizmann Institute of Science)

  • Tamar Unger

    (Weizmann Institute of Science)

  • Shira Albeck

    (Weizmann Institute of Science)

  • Camilo Aponte-Santamaria

    (Heidelberg Institute for Theoretical Studies (HITS)
    Heidelberg University, Mathematikon, INF 205)

  • Sergi Garcia-Manyes

    (King’s College London
    The Francis Crick Institute)

  • Ohad Medalia

    (University of Zurich)

  • Benjamin Geiger

    (Weizmann Institute of Science)

  • Frauke Gräter

    (Heidelberg Institute for Theoretical Studies (HITS)
    Heidelberg University, Mathematikon, INF 205
    Heidelberg University, INF 225)

Abstract

The talin-vinculin axis is a key mechanosensing component of cellular focal adhesions. How talin and vinculin respond to forces and regulate one another remains unclear. By combining single-molecule magnetic tweezers experiments, Molecular Dynamics simulations, actin-bundling assays, and adhesion assembly experiments in live cells, we here describe a two-ways allosteric network within vinculin as a regulator of the talin-vinculin interaction. We directly observe a maturation process of vinculin upon talin binding, which reinforces the binding to talin at a rate of 0.03 s−1. This allosteric transition can compete with force-induced dissociation of vinculin from talin only at forces up to 10 pN. Mimicking the allosteric activation by mutation yields a vinculin molecule that bundles actin and localizes to focal adhesions in a force-independent manner. Hence, the allosteric switch confines talin-vinculin interactions and focal adhesion build-up to intermediate force levels. The ‘allosteric vinculin mutant’ is a valuable molecular tool to further dissect the mechanical and biochemical signalling circuits at focal adhesions and elsewhere.

Suggested Citation

  • Florian Franz & Rafael Tapia-Rojo & Sabina Winograd-Katz & Rajaa Boujemaa-Paterski & Wenhong Li & Tamar Unger & Shira Albeck & Camilo Aponte-Santamaria & Sergi Garcia-Manyes & Ohad Medalia & Benjamin , 2023. "Allosteric activation of vinculin by talin," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39646-4
    DOI: 10.1038/s41467-023-39646-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39646-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-39646-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Mingxi Yao & Benjamin T. Goult & Benjamin Klapholz & Xian Hu & Christopher P. Toseland & Yingjian Guo & Peiwen Cong & Michael P. Sheetz & Jie Yan, 2016. "The mechanical response of talin," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    2. Shubhasis Haldar & Rafael Tapia-Rojo & Edward C. Eckels & Jessica Valle-Orero & Julio M. Fernandez, 2017. "Trigger factor chaperone acts as a mechanical foldase," Nature Communications, Nature, vol. 8(1), pages 1-7, December.
    3. Tina Izard & Gwyndaf Evans & Robert A. Borgon & Christina L. Rush & Gerard Bricogne & Philippe R. J. Bois, 2004. "Vinculin activation by talin through helical bundle conversion," Nature, Nature, vol. 427(6970), pages 171-175, January.
    4. Carsten Grashoff & Brenton D. Hoffman & Michael D. Brenner & Ruobo Zhou & Maddy Parsons & Michael T. Yang & Mark A. McLean & Stephen G. Sligar & Christopher S. Chen & Taekjip Ha & Martin A. Schwartz, 2010. "Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics," Nature, Nature, vol. 466(7303), pages 263-266, July.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Erumbi S. Rangarajan & Julian L. Bois & Scott B. Hansen & Tina Izard, 2024. "High-resolution snapshots of the talin auto-inhibitory states suggest roles in cell adhesion and signaling," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Hong Wang & Rayan Said & Clémence Nguyen-Vigouroux & Véronique Henriot & Peter Gebhardt & Julien Pernier & Robert Grosse & Christophe Le Clainche, 2024. "Talin and vinculin combine their activities to trigger actin assembly," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Jiankai Wei & Wei Zhang & An Jiang & Hongzhe Peng & Quanyong Zhang & Yuting Li & Jianqing Bi & Linting Wang & Penghui Liu & Jing Wang & Yonghang Ge & Liya Zhang & Haiyan Yu & Lei Li & Shi Wang & Liang, 2024. "Temporospatial hierarchy and allele-specific expression of zygotic genome activation revealed by distant interspecific urochordate hybrids," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. Estera Merljak & Benjamin Malovrh & Roman Jerala, 2023. "Segmentation strategy of de novo designed four-helical bundles expands protein oligomerization modalities for cell regulation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Sawako Yamashiro & David M. Rutkowski & Kelli Ann Lynch & Ying Liu & Dimitrios Vavylonis & Naoki Watanabe, 2023. "Force transmission by retrograde actin flow-induced dynamic molecular stretching of Talin," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Daniel A. Nissley & Yang Jiang & Fabio Trovato & Ian Sitarik & Karthik B. Narayan & Philip To & Yingzi Xia & Stephen D. Fried & Edward P. O’Brien, 2022. "Universal protein misfolding intermediates can bypass the proteostasis network and remain soluble and less functional," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Thomas Litschel & Charlotte F. Kelley & Xiaohang Cheng & Leon Babl & Naoko Mizuno & Lindsay B. Case & Petra Schwille, 2024. "Membrane-induced 2D phase separation of the focal adhesion protein talin," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    8. Serena Petracchini & Daniel Hamaoui & Anne Doye & Atef Asnacios & Florian Fage & Elisa Vitiello & Martial Balland & Sebastien Janel & Frank Lafont & Mukund Gupta & Benoit Ladoux & Jerôme Gilleron & Te, 2022. "Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    9. Yuhang Zhang & Jingyi Du & Xian Liu & Fei Shang & Yunxin Deng & Jiaqing Ye & Yukai Wang & Jie Yan & Hu Chen & Miao Yu & Shimin Le, 2024. "Multi-domain interaction mediated strength-building in human α-actinin dimers unveiled by direct single-molecule quantification," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    10. Venkat R. Chirasani & Mohammad Ashhar I. Khan & Juilee N. Malavade & Nikolay V. Dokholyan & Brenton D. Hoffman & Sharon L. Campbell, 2023. "Molecular basis and cellular functions of vinculin-actin directional catch bonding," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    11. Matthew R. Pawlak & Adam T. Smiley & Maria Paz Ramirez & Marcus D. Kelly & Ghaidan A. Shamsan & Sarah M. Anderson & Branden A. Smeester & David A. Largaespada & David J. Odde & Wendy R. Gordon, 2023. "RAD-TGTs: high-throughput measurement of cellular mechanotype via rupture and delivery of DNA tension probes," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    12. Brooke E. Danielsson & Bobin George Abraham & Elina Mäntylä & Jolene I. Cabe & Carl R. Mayer & Anna Rekonen & Frans Ek & Daniel E. Conway & Teemu O. Ihalainen, 2023. "Nuclear lamina strain states revealed by intermolecular force biosensor," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    13. Andrea Braeutigam & Ahmet Nihat Simsek & Gerhard Gompper & Benedikt Sabass, 2022. "Generic self-stabilization mechanism for biomolecular adhesions under load," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    14. Maximilian Huber & Javier Casares-Arias & Reinhard Fässler & Daniel J. Müller & Nico Strohmeyer, 2023. "In mitosis integrins reduce adhesion to extracellular matrix and strengthen adhesion to adjacent cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    15. Chrystian Junqueira Alves & Rafael Dariolli & Jonathan Haydak & Sangjo Kang & Theodore Hannah & Robert J. Wiener & Stefanie DeFronzo & Rut Tejero & Gabriele L. Gusella & Aarthi Ramakrishnan & Rodrigo , 2021. "Plexin-B2 orchestrates collective stem cell dynamics via actomyosin contractility, cytoskeletal tension and adhesion," Nature Communications, Nature, vol. 12(1), pages 1-23, December.
    16. Sorosh Amiri & Camelia Muresan & Xingbo Shang & Clotilde Huet-Calderwood & Martin A. Schwartz & David A. Calderwood & Michael Murrell, 2023. "Intracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39646-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.