IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28974-6.html
   My bibliography  Save this article

Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2

Author

Listed:
  • Clement Verkest

    (University Medical Center Hamburg-Eppendorf)

  • Irina Schaefer

    (Heidelberg University)

  • Timo A. Nees

    (Heidelberg University
    Heidelberg University Hospital)

  • Na Wang

    (Heidelberg University)

  • Juri M. Jegelka

    (Heidelberg University)

  • Francisco J. Taberner

    (Heidelberg University
    Universidad Miguel Hernández – CSIC)

  • Stefan G. Lechner

    (University Medical Center Hamburg-Eppendorf
    Heidelberg University)

Abstract

A central question in mechanobiology is how mechanical forces acting in or on cells are transmitted to mechanically-gated PIEZO channels that convert these forces into biochemical signals. Here we examined the role of the intracellular domains of PIEZO2, which account for 25% of the channel, and demonstrate that these domains fine-tune properties such as poking and stretch-sensitivity, velocity coding and single channel conductance. Moreover, we show that the intrinsically disordered linker between the transmembrane helices twelve and thirteen (IDR5) is required for the activation of PIEZO2 by cytoskeleton-transmitted forces. The deletion of IDR5 abolishes PIEZO2-mediated inhibition of neurite outgrowth, while it only partially affected its sensitivity to cell indentation and does not alter its stretch sensitivity. Thus, we propose that PIEZO2 is a polymodal mechanosensor that detects different types of mechanical stimuli via different force transmission pathways, which highlights the importance of utilizing multiple complementary assays when investigating PIEZO function.

Suggested Citation

  • Clement Verkest & Irina Schaefer & Timo A. Nees & Na Wang & Juri M. Jegelka & Francisco J. Taberner & Stefan G. Lechner, 2022. "Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28974-6
    DOI: 10.1038/s41467-022-28974-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28974-6
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-28974-6?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. Li Wang & Heng Zhou & Mingmin Zhang & Wenhao Liu & Tuan Deng & Qiancheng Zhao & Yiran Li & Jianlin Lei & Xueming Li & Bailong Xiao, 2019. "Structure and mechanogating of the mammalian tactile channel PIEZO2," Nature, Nature, vol. 573(7773), pages 225-229, September.
    2. Thorsten Wagner & Alexandra Kroll & Chandrashekara R Haramagatti & Hans-Gerd Lipinski & Martin Wiemann, 2017. "Classification and Segmentation of Nanoparticle Diffusion Trajectories in Cellular Micro Environments," PLOS ONE, Public Library of Science, vol. 12(1), pages 1-20, January.
    3. Charles D. Cox & Chilman Bae & Lynn Ziegler & Silas Hartley & Vesna Nikolova-Krstevski & Paul R. Rohde & Chai-Ann Ng & Frederick Sachs & Philip A. Gottlieb & Boris Martinac, 2016. "Removal of the mechanoprotective influence of the cytoskeleton reveals PIEZO1 is gated by bilayer tension," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    4. Luis O. Romero & Rebeca Caires & Alec R. Nickolls & Alexander T. Chesler & Julio F. Cordero-Morales & Valeria Vásquez, 2020. "A dietary fatty acid counteracts neuronal mechanical sensitization," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    5. Sanjeev S. Ranade & Seung-Hyun Woo & Adrienne E. Dubin & Rabih A. Moshourab & Christiane Wetzel & Matt Petrus & Jayanti Mathur & Valérie Bégay & Bertrand Coste & James Mainquist & A. J. Wilson & Allai, 2014. "Piezo2 is the major transducer of mechanical forces for touch sensation in mice," Nature, Nature, vol. 516(7529), pages 121-125, December.
    6. Mirko Moroni & M. Rocio Servin-Vences & Raluca Fleischer & Oscar Sánchez-Carranza & Gary R. Lewin, 2018. "Voltage gating of mechanosensitive PIEZO channels," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    7. J. M. Kefauver & A. B. Ward & A. Patapoutian, 2020. "Discoveries in structure and physiology of mechanically activated ion channels," Nature, Nature, vol. 587(7835), pages 567-576, November.
    8. Yanfeng Wang & Shaopeng Chi & Huifang Guo & Guang Li & Li Wang & Qiancheng Zhao & Yu Rao & Liansuo Zu & Wei He & Bailong Xiao, 2018. "A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    9. Srdjan Maksimovic & Masashi Nakatani & Yoshichika Baba & Aislyn M. Nelson & Kara L. Marshall & Scott A. Wellnitz & Pervez Firozi & Seung-Hyun Woo & Sanjeev Ranade & Ardem Patapoutian & Ellen A. Lumpki, 2014. "Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors," Nature, Nature, vol. 509(7502), pages 617-621, May.
    10. Jiae Lee & Alejandra J. H. Cabrera & Cecilia M. T. Nguyen & Young V. Kwon, 2020. "Dissemination of RasV12-transformed cells requires the mechanosensitive channel Piezo," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    11. Jason Wu & Raman Goyal & Jörg Grandl, 2016. "Localized force application reveals mechanically sensitive domains of Piezo1," Nature Communications, Nature, vol. 7(1), pages 1-10, December.
    12. N Eijkelkamp & J.E. Linley & J.M. Torres & L. Bee & A.H. Dickenson & M. Gringhuis & M.S. Minett & G.S. Hong & E. Lee & U. Oh & Y. Ishikawa & F.J. Zwartkuis & J.J. Cox & J.N. Wood, 2013. "A role for Piezo2 in EPAC1-dependent mechanical allodynia," Nature Communications, Nature, vol. 4(1), pages 1-13, June.
    13. Kara L. Marshall & Dimah Saade & Nima Ghitani & Adam M. Coombs & Marcin Szczot & Jason Keller & Tracy Ogata & Ihab Daou & Lisa T. Stowers & Carsten G. Bönnemann & Alexander T. Chesler & Ardem Patapout, 2020. "PIEZO2 in sensory neurons and urothelial cells coordinates urination," Nature, Nature, vol. 588(7837), pages 290-295, December.
    14. Luis O. Romero & Rebeca Caires & Alec R. Nickolls & Alexander T. Chesler & Julio F. Cordero-Morales & Valeria Vásquez, 2020. "Publisher Correction: A dietary fatty acid counteracts neuronal mechanical sensitization," Nature Communications, Nature, vol. 11(1), pages 1-1, December.
    15. Keiko Nonomura & Seung-Hyun Woo & Rui B. Chang & Astrid Gillich & Zhaozhu Qiu & Allain G. Francisco & Sanjeev S. Ranade & Stephen D. Liberles & Ardem Patapoutian, 2017. "Piezo2 senses airway stretch and mediates lung inflation-induced apnoea," Nature, Nature, vol. 541(7636), pages 176-181, January.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Shilong Yang & Xinwen Miao & Steven Arnold & Boxuan Li & Alan T. Ly & Huan Wang & Matthew Wang & Xiangfu Guo & Medha M. Pathak & Wenting Zhao & Charles D. Cox & Zheng Shi, 2022. "Membrane curvature governs the distribution of Piezo1 in live cells," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Benedikt Goretzki & Christoph Wiedemann & Brett A. McCray & Stefan L. Schäfer & Jasmin Jansen & Frederike Tebbe & Sarah-Ana Mitrovic & Julia Nöth & Ainara Claveras Cabezudo & Jack K. Donohue & Cy M. J, 2023. "Crosstalk between regulatory elements in disordered TRPV4 N-terminus modulates lipid-dependent channel activity," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Matthew Gabrielle & Yevgen Yudin & Yujue Wang & Xiaoyang Su & Tibor Rohacs, 2024. "Phosphatidic acid is an endogenous negative regulator of PIEZO2 channels and mechanical sensitivity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Yi-Yu Lin & Yan Lu & Chun-Yun Li & Xue-Fei Ma & Miao-Qing Shao & Yu-Hao Gao & Yu-Qing Zhang & Hai-Ning Jiang & Yan Liu & Yang Yang & Li-Dong Huang & Peng Cao & Heng-Shan Wang & Jin Wang & Ye Yu, 2024. "Finely ordered intracellular domain harbors an allosteric site to modulate physiopathological function of P2X3 receptors," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    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. Luis O. Romero & Rebeca Caires & A. Kaitlyn Victor & Juanma Ramirez & Francisco J. Sierra-Valdez & Patrick Walsh & Vincent Truong & Jungsoo Lee & Ugo Mayor & Lawrence T. Reiter & Valeria Vásquez & Jul, 2023. "Linoleic acid improves PIEZO2 dysfunction in a mouse model of Angelman Syndrome," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Matthew Gabrielle & Yevgen Yudin & Yujue Wang & Xiaoyang Su & Tibor Rohacs, 2024. "Phosphatidic acid is an endogenous negative regulator of PIEZO2 channels and mechanical sensitivity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Shilong Yang & Xinwen Miao & Steven Arnold & Boxuan Li & Alan T. Ly & Huan Wang & Matthew Wang & Xiangfu Guo & Medha M. Pathak & Wenting Zhao & Charles D. Cox & Zheng Shi, 2022. "Membrane curvature governs the distribution of Piezo1 in live cells," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Jonathan Madar & Namrata Tiwari & Cristina Smith & Divya Sharma & Shanwei Shen & Alsiddig Elmahdi & Liya Y. Qiao, 2023. "Piezo2 regulates colonic mechanical sensitivity in a sex specific manner in mice," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Alia M. Obeidat & Matthew J. Wood & Natalie S. Adamczyk & Shingo Ishihara & Jun Li & Lai Wang & Dongjun Ren & David A. Bennett & Richard J. Miller & Anne-Marie Malfait & Rachel E. Miller, 2023. "Piezo2 expressing nociceptors mediate mechanical sensitization in experimental osteoarthritis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Martina Nicoletti & Letizia Chiodo & Alessandro Loppini, 2021. "Biophysics and Modeling of Mechanotransduction in Neurons: A Review," Mathematics, MDPI, vol. 9(4), pages 1-32, February.
    7. Francisco Andrés Peralta & Mélaine Balcon & Adeline Martz & Deniza Biljali & Federico Cevoli & Benoit Arnould & Antoine Taly & Thierry Chataigneau & Thomas Grutter, 2023. "Optical control of PIEZO1 channels," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Nathalia G. Amado & Elena D. Nosyreva & David Thompson & Thomas J. Egeland & Osita W. Ogujiofor & Michelle Yang & Alexandria N. Fusco & Niccolo Passoni & Jeremy Mathews & Brandi Cantarel & Linda A. Ba, 2024. "PIEZO1 loss-of-function compound heterozygous mutations in the rare congenital human disorder Prune Belly Syndrome," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    9. Mingfeng Zhang & Yuanyue Shan & Charles D. Cox & Duanqing Pei, 2023. "A mechanical-coupling mechanism in OSCA/TMEM63 channel mechanosensitivity," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    10. Julia Ojeda-Alonso & Laura Calvo-Enrique & Ricardo Paricio-Montesinos & Rakesh Kumar & Ming-Dong Zhang & James F. A. Poulet & Patrik Ernfors & Gary R. Lewin, 2024. "Sensory Schwann cells set perceptual thresholds for touch and selectively regulate mechanical nociception," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    11. Gregory J Gerling & Lingtian Wan & Benjamin U Hoffman & Yuxiang Wang & Ellen A Lumpkin, 2018. "Computation predicts rapidly adapting mechanotransduction currents cannot account for tactile encoding in Merkel cell-neurite complexes," PLOS Computational Biology, Public Library of Science, vol. 14(6), pages 1-21, June.
    12. Elvis K. Boahen & Baohai Pan & Hyukmin Kweon & Joo Sung Kim & Hanbin Choi & Zhengyang Kong & Dong Jun Kim & Jin Zhu & Wu Bin Ying & Kyung Jin Lee & Do Hwan Kim, 2022. "Ultrafast, autonomous self-healable iontronic skin exhibiting piezo-ionic dynamics," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    13. Wang, Xiaolong & Feng, Jing & Liu, Qi & Li, Yongge & Xu, Yong, 2022. "Neural network-based parameter estimation of stochastic differential equations driven by Lévy noise," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 606(C).
    14. Mayank Gautam & Akihiro Yamada & Ayaka I. Yamada & Qinxue Wu & Kim Kridsada & Jennifer Ling & Huasheng Yu & Peter Dong & Minghong Ma & Jianguo Gu & Wenqin Luo, 2024. "Distinct local and global functions of mouse Aβ low-threshold mechanoreceptors in mechanical nociception," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    15. Steven M Barlow & Rebecca Custead, 2019. "Vibrography: Single-Interval Up/Down (SIUD) Adaptive Vibrotactile Threshold Estimation of the Glabrous Hand and Perioral Face in Neurotypical Adults," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 22(4), pages 16837-16847, November.
    16. Sine Yaganoglu & Konstantinos Kalyviotis & Christina Vagena-Pantoula & Dörthe Jülich & Benjamin M. Gaub & Maaike Welling & Tatiana Lopes & Dariusz Lachowski & See Swee Tang & Armando Del Rio Hernandez, 2023. "Highly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    17. Yuanyuan Zhao & Ju Liu & Gang Lu & Jinliang Zhang & Liyang Wan & Shan Peng & Chao Li & Yanlei Wang & Mingzhan Wang & Hongyan He & John H. Xin & Yulong Ding & Shuang Zheng, 2024. "Diurnal humidity cycle driven selective ion transport across clustered polycation membrane," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    18. Aleksandra Grzesiek & Radosław Zimroz & Paweł Śliwiński & Norbert Gomolla & Agnieszka Wyłomańska, 2021. "A Method for Structure Breaking Point Detection in Engine Oil Pressure Data," Energies, MDPI, vol. 14(17), pages 1-24, September.
    19. Jonathan Mount & Grigory Maksaev & Brock T. Summers & James A. J. Fitzpatrick & Peng Yuan, 2022. "Structural basis for mechanotransduction in a potassium-dependent mechanosensitive ion channel," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    20. Amandeep Kaur & Madhu & Alok Sharma & Kashmir Singh & Santosh Kumar Upadhyay, 2023. "Exploration of Piezo Channels in Bread Wheat ( Triticum aestivum L.)," Agriculture, MDPI, vol. 13(4), pages 1-16, March.

    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:13:y:2022:i:1:d:10.1038_s41467-022-28974-6. 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.