IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-52581-2.html
   My bibliography  Save this article

High-resolution snapshots of the talin auto-inhibitory states suggest roles in cell adhesion and signaling

Author

Listed:
  • Erumbi S. Rangarajan

    (UF Scripps
    UF Scripps)

  • Julian L. Bois

    (UF Scripps)

  • Scott B. Hansen

    (UF Scripps
    The Scripps Research Institute)

  • Tina Izard

    (UF Scripps
    UF Scripps
    The Scripps Research Institute)

Abstract

Talin regulates crucial cellular functions, including cell adhesion and motility, and affects human diseases. Triggered by mechanical forces, talin plays crucial roles in facilitating the formation of focal adhesions and recruiting essential focal adhesion regulatory elements such as vinculin. The structural flexibility allows talin to fine-tune its signaling responses. This study presents our 2.7 Å cryoEM structures of talin, which surprisingly uncovers several auto-inhibitory states. Contrary to previous suggestions, our structures reveal that (1) the first and last three domains are not involved in maintaining talin in its closed state and are mobile, (2) the talin F-actin and membrane binding domain are loosely attached and thus available for binding, and (3) the main force-sensing domain is oriented with its vinculin binding sites ready for release. These structural snapshots offer insights and advancements in understanding the dynamic talin activation mechanism, which is crucial for mediating cell adhesion.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52581-2
    DOI: 10.1038/s41467-024-52581-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-52581-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-52581-2?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. Gilbert Di Paolo & Lorenzo Pellegrini & Kresimir Letinic & Gianluca Cestra & Roberto Zoncu & Sergei Voronov & Sunghoe Chang & Jun Guo & Markus R. Wenk & Pietro De Camilli, 2002. "Recruitment and regulation of phosphatidylinositol phosphate kinase type 1γ by the FERM domain of talin," Nature, Nature, vol. 420(6911), pages 85-89, November.
    2. 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.
    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. Tristan Bepler & Kotaro Kelley & Alex J. Noble & Bonnie Berger, 2020. "Topaz-Denoise: general deep denoising models for cryoEM and cryoET," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    5. Guoying Jiang & Grégory Giannone & David R. Critchley & Emiko Fukumoto & Michael P. Sheetz, 2003. "Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin," Nature, Nature, vol. 424(6946), pages 334-337, July.
    6. E. Nicholas Petersen & Hae-Won Chung & Arman Nayebosadri & Scott B. Hansen, 2016. "Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D," Nature Communications, Nature, vol. 7(1), pages 1-8, December.
    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. 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.
    2. Fan Lu & Liang Zhu & Thomas Bromberger & Jun Yang & Qiannan Yang & Jianmin Liu & Edward F. Plow & Markus Moser & Jun Qin, 2022. "Mechanism of integrin activation by talin and its cooperation with kindlin," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    3. Xinyu Zhang & Tianfang Zhao & Jiansheng Chen & Yuan Shen & Xueming Li, 2022. "EPicker is an exemplar-based continual learning approach for knowledge accumulation in cryoEM particle picking," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    4. Simon Wiedemann & Reinhard Heckel, 2024. "A deep learning method for simultaneous denoising and missing wedge reconstruction in cryogenic electron tomography," Nature Communications, Nature, vol. 15(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. 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.
    7. Luka Bacic & Guillaume Gaullier & Jugal Mohapatra & Guanzhong Mao & Klaus Brackmann & Mikhail Panfilov & Glen Liszczak & Anton Sabantsev & Sebastian Deindl, 2024. "Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    8. 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.
    9. Yaejin Yun & Hyeongseop Jeong & Thibaut Laboute & Kirill A. Martemyanov & Hyung Ho Lee, 2024. "Cryo-EM structure of human class C orphan GPCR GPR179 involved in visual processing," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    10. Leishu Lin & Jiayuan Dong & Shun Xu & Jinman Xiao & Cong Yu & Fengfeng Niu & Zhiyi Wei, 2024. "Autoinhibition and relief mechanisms for MICAL monooxygenases in F-actin disassembly," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    11. Sriram Aiyer & Philip R. Baldwin & Shi Min Tan & Zelin Shan & Juntaek Oh & Atousa Mehrani & Marianne E. Bowman & Gordon Louie & Dario Oliveira Passos & Selena Đorđević-Marquardt & Mario Mietzsch & Jos, 2024. "Overcoming resolution attenuation during tilted cryo-EM data collection," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    12. Benjamin C. Creekmore & Kathryn Kixmoeller & Ben E. Black & Edward B. Lee & Yi-Wei Chang, 2024. "Ultrastructure of human brain tissue vitrified from autopsy revealed by cryo-ET with cryo-plasma FIB milling," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    13. Michael Kugler & Felix J. Metzner & Gregor Witte & Karl-Peter Hopfner & Katja Lammens, 2024. "Phosphorylation-mediated conformational change regulates human SLFN11," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    14. Michal Dudek & Dharshika R. J. Pathiranage & Beatriz Bano-Otalora & Anna Paszek & Natalie Rogers & Cátia F. Gonçalves & Craig Lawless & Dong Wang & Zhuojing Luo & Liu Yang & Farshid Guilak & Judith A., 2023. "Mechanical loading and hyperosmolarity as a daily resetting cue for skeletal circadian clocks," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    15. Kathryn H. Gunn & Saskia B. Neher, 2023. "Structure of dimeric lipoprotein lipase reveals a pore adjacent to the active site," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    16. Alison B. Hickman & Laurie Lannes & Christopher M. Furman & Christina Hong & Lidiya Franklin & Rodolfo Ghirlando & Arpita Ghosh & Wentian Luo & Parthena Konstantinidou & Hernán A. Lorenzi & Anne Grove, 2025. "Activity of the mammalian DNA transposon piggyBat from Myotis lucifugus is restricted by its own transposon ends," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    17. Kotaro Kelley & Ashleigh M. Raczkowski & Oleg Klykov & Pattana Jaroenlak & Daija Bobe & Mykhailo Kopylov & Edward T. Eng & Gira Bhabha & Clinton S. Potter & Bridget Carragher & Alex J. Noble, 2022. "Waffle Method: A general and flexible approach for improving throughput in FIB-milling," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    18. Cecile O Mejean & Andrew W Schaefer & Kenneth B Buck & Holger Kress & Alla Shundrovsky & Jason W Merrill & Eric R Dufresne & Paul Forscher, 2013. "Elastic Coupling of Nascent apCAM Adhesions to Flowing Actin Networks," PLOS ONE, Public Library of Science, vol. 8(9), pages 1-1, September.
    19. Ryo Nagao & Koji Kato & Tasuku Hamaguchi & Yoshifumi Ueno & Naoki Tsuboshita & Shota Shimizu & Miyu Furutani & Shigeki Ehira & Yoshiki Nakajima & Keisuke Kawakami & Takehiro Suzuki & Naoshi Dohmae & S, 2023. "Structure of a monomeric photosystem I core associated with iron-stress-induced-A proteins from Anabaena sp. PCC 7120," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    20. Riley D. Metcalfe & Juliana A. Martinez Fiesco & Luis Bonet-Ponce & Jillian H. Kluss & Mark R. Cookson & Ping Zhang, 2023. "Structure and regulation of full-length human leucine-rich repeat kinase 1," Nature Communications, Nature, vol. 14(1), pages 1-17, 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:15:y:2024:i:1:d:10.1038_s41467-024-52581-2. 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.