IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34298-2.html
   My bibliography  Save this article

Spatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival

Author

Listed:
  • Joanne Watson

    (The University of Manchester
    The University of Manchester)

  • Harriet R. Ferguson

    (The University of Manchester)

  • Rosie M. Brady

    (The University of Manchester)

  • Jennifer Ferguson

    (The University of Manchester)

  • Paul Fullwood

    (The University of Manchester)

  • Hanyi Mo

    (The University of Manchester)

  • Katherine H. Bexley

    (The University of Manchester)

  • David Knight

    (The University of Manchester)

  • Gareth Howell

    (The University of Manchester)

  • Jean-Marc Schwartz

    (The University of Manchester)

  • Michael P. Smith

    (The University of Manchester)

  • Chiara Francavilla

    (The University of Manchester
    The University of Manchester)

Abstract

Receptor Tyrosine Kinase (RTK) endocytosis-dependent signalling drives cell proliferation and motility during development and adult homeostasis, but is dysregulated in diseases, including cancer. The recruitment of RTK signalling partners during endocytosis, specifically during recycling to the plasma membrane, is still unknown. Focusing on Fibroblast Growth Factor Receptor 2b (FGFR2b) recycling, we reveal FGFR signalling partners proximal to recycling endosomes by developing a Spatially Resolved Phosphoproteomics (SRP) approach based on APEX2-driven biotinylation followed by phosphorylated peptides enrichment. Combining this with traditional phosphoproteomics, bioinformatics, and targeted assays, we uncover that FGFR2b stimulated by its recycling ligand FGF10 activates mTOR-dependent signalling and ULK1 at the recycling endosomes, leading to autophagy suppression and cell survival. This adds to the growing importance of RTK recycling in orchestrating cell fate and suggests a therapeutically targetable vulnerability in ligand-responsive cancer cells. Integrating SRP with other systems biology approaches provides a powerful tool to spatially resolve cellular signalling.

Suggested Citation

  • Joanne Watson & Harriet R. Ferguson & Rosie M. Brady & Jennifer Ferguson & Paul Fullwood & Hanyi Mo & Katherine H. Bexley & David Knight & Gareth Howell & Jean-Marc Schwartz & Michael P. Smith & Chiar, 2022. "Spatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34298-2
    DOI: 10.1038/s41467-022-34298-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34298-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-34298-2?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. Avraham Ashkenazi & Carla F. Bento & Thomas Ricketts & Mariella Vicinanza & Farah Siddiqi & Mariana Pavel & Ferdinando Squitieri & Maarten C. Hardenberg & Sara Imarisio & Fiona M. Menzies & David C. R, 2017. "Polyglutamine tracts regulate beclin 1-dependent autophagy," Nature, Nature, vol. 545(7652), pages 108-111, May.
    2. Wei Qin & Samuel A. Myers & Dominique K. Carey & Steven A. Carr & Alice Y. Ting, 2021. "Spatiotemporally-resolved mapping of RNA binding proteins via functional proximity labeling reveals a mitochondrial mRNA anchor promoting stress recovery," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    3. Ana Martinez-Val & Dorte B. Bekker-Jensen & Sophia Steigerwald & Claire Koenig & Ole Østergaard & Adi Mehta & Trung Tran & Krzysztof Sikorski & Estefanía Torres-Vega & Ewa Kwasniewicz & Sólveig Hlín B, 2021. "Spatial-proteomics reveals phospho-signaling dynamics at subcellular resolution," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    4. Christopher D. Go & James D. R. Knight & Archita Rajasekharan & Bhavisha Rathod & Geoffrey G. Hesketh & Kento T. Abe & Ji-Young Youn & Payman Samavarchi-Tehrani & Hui Zhang & Lucie Y. Zhu & Evelyn Pop, 2021. "A proximity-dependent biotinylation map of a human cell," Nature, Nature, vol. 595(7865), pages 120-124, July.
    5. Laura Cinque & Alison Forrester & Rosa Bartolomeo & Maria Svelto & Rossella Venditti & Sandro Montefusco & Elena Polishchuk & Edoardo Nusco & Antonio Rossi & Diego L. Medina & Roman Polishchuk & Maria, 2015. "FGF signalling regulates bone growth through autophagy," Nature, Nature, vol. 528(7581), pages 272-275, 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. Julia P. Schessner & Vincent Albrecht & Alexandra K. Davies & Pavel Sinitcyn & Georg H. H. Borner, 2023. "Deep and fast label-free Dynamic Organellar Mapping," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Jasjot Singh & Hadeer Elhabashy & Pathma Muthukottiappan & Markus Stepath & Martin Eisenacher & Oliver Kohlbacher & Volkmar Gieselmann & Dominic Winter, 2022. "Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Haofan Sun & Bin Fu & Xiaohong Qian & Ping Xu & Weijie Qin, 2024. "Nuclear and cytoplasmic specific RNA binding proteome enrichment and its changes upon ferroptosis induction," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Julian Petersen & Lukas Englmaier & Artem V. Artemov & Irina Poverennaya & Ruba Mahmoud & Thibault Bouderlique & Marketa Tesarova & Ruslan Deviatiiarov & Anett Szilvásy-Szabó & Evgeny E. Akkuratov & D, 2023. "A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    5. Donghua Hu & Min Tan & Dongliang Lu & Brian Kleiboeker & Xuejing Liu & Hongsuk Park & Alexxai V. Kravitz & Kooresh I. Shoghi & Yu-Hua Tseng & Babak Razani & Akihiro Ikeda & Irfan J. Lodhi, 2023. "TMEM135 links peroxisomes to the regulation of brown fat mitochondrial fission and energy homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    6. Patricia González-Rodríguez & Daniel J. Klionsky & Bertrand Joseph, 2022. "Autophagy regulation by RNA alternative splicing and implications in human diseases," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Henrik M. Hammarén & Eva-Maria Geissen & Clement M. Potel & Martin Beck & Mikhail M. Savitski, 2022. "Protein-Peptide Turnover Profiling reveals the order of PTM addition and removal during protein maturation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Lidia Wrobel & Sandra M. Hill & Alvin Djajadikerta & Marian Fernandez-Estevez & Cansu Karabiyik & Avraham Ashkenazi & Victoria J. Barratt & Eleanna Stamatakou & Anders Gunnarsson & Timothy Rasmusson &, 2022. "Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    9. Kohdai Yamada & Ryouhei Shioya & Kohei Nishino & Hirotake Furihata & Atsushi Hijikata & Mika K. Kaneko & Yukinari Kato & Tsuyoshi Shirai & Hidetaka Kosako & Tatsuya Sawasaki, 2023. "Proximity extracellular protein-protein interaction analysis of EGFR using AirID-conjugated fragment of antigen binding," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    10. JohnCarlo Kristofich & Christopher V. Nicchitta, 2023. "Signal-noise metrics for RNA binding protein identification reveal broad spectrum protein-RNA interaction frequencies and dynamics," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    11. Chiara Parodi & Jonathan A Hardman & Giulia Allavena & Roberto Marotta & Tiziano Catelani & Marta Bertolini & Ralf Paus & Benedetto Grimaldi, 2018. "Autophagy is essential for maintaining the growth of a human (mini-)organ: Evidence from scalp hair follicle organ culture," PLOS Biology, Public Library of Science, vol. 16(3), pages 1-22, March.
    12. Ying Zhu & Kerem Can Akkaya & Julia Ruta & Nanako Yokoyama & Cong Wang & Max Ruwolt & Diogo Borges Lima & Martin Lehmann & Fan Liu, 2024. "Cross-link assisted spatial proteomics to map sub-organelle proteomes and membrane protein topologies," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    13. Rahul Kumar & Maleeha Khan & Vincent Francis & Adriana Aguila & Gopinath Kulasekaran & Emily Banks & Peter S. McPherson, 2024. "DENND6A links Arl8b to a Rab34/RILP/dynein complex, regulating lysosomal positioning and autophagy," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    14. Maik Müller & Fabienne Gräbnitz & Niculò Barandun & Yang Shen & Fabian Wendt & Sebastian N. Steiner & Yannik Severin & Stefan U. Vetterli & Milon Mondal & James R. Prudent & Raphael Hofmann & Marc Oos, 2021. "Light-mediated discovery of surfaceome nanoscale organization and intercellular receptor interaction networks," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    15. Wenbin Xu & Han Yao & Zhen Wu & Xiaojun Yan & Zishan Jiao & Yajing Liu & Meng Zhang & Donglai Wang, 2024. "Oncoprotein SET-associated transcription factor ZBTB11 triggers lung cancer metastasis," Nature Communications, Nature, vol. 15(1), pages 1-21, 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:13:y:2022:i:1:d:10.1038_s41467-022-34298-2. 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.