IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-35908-3.html
   My bibliography  Save this article

Tyrosyl-tRNA synthetase has a noncanonical function in actin bundling

Author

Listed:
  • Biljana Ermanoska

    (University of Antwerp
    University of Antwerp
    Brandeis University)

  • Bob Asselbergh

    (VIB Center for Molecular Neurology, VIB
    University of Antwerp)

  • Laura Morant

    (University of Antwerp
    University of Antwerp)

  • Maria-Luise Petrovic-Erfurth

    (University of Antwerp
    University of Antwerp)

  • Seyyedmohsen Hosseinibarkooie

    (University Hospital of Cologne; University of Cologne
    University of Virginia)

  • Ricardo Leitão-Gonçalves

    (University of Antwerp
    University of Antwerp
    Frontiers Media SA)

  • Leonardo Almeida-Souza

    (University of Antwerp
    University of Antwerp
    University of Helsinki)

  • Sven Bervoets

    (University of Antwerp
    University of Antwerp
    University of Utah)

  • Litao Sun

    (The Scripps Research Institute
    Sun Yat-Sen University)

  • LaTasha Lee

    (Florida Atlantic University
    National Minority Quality Forum)

  • Derek Atkinson

    (University of Antwerp
    University of Antwerp
    Max Planck Institute of Immunobiology and Epigenetics)

  • Akram Khanghahi

    (University of Antwerp
    University of Antwerp)

  • Ivaylo Tournev

    (Medical University-Sofia
    New Bulgarian University)

  • Patrick Callaerts

    (KU Leuven)

  • Patrik Verstreken

    (VIB-KU Leuven Center for Brain & Disease Research
    Leuven Brain Institute, Mission Lucidity)

  • Xiang-Lei Yang

    (The Scripps Research Institute)

  • Brunhilde Wirth

    (University Hospital of Cologne; University of Cologne)

  • Avital A. Rodal

    (Brandeis University)

  • Vincent Timmerman

    (University of Antwerp)

  • Bruce L. Goode

    (Brandeis University)

  • Tanja A. Godenschwege

    (Florida Atlantic University)

  • Albena Jordanova

    (University of Antwerp
    University of Antwerp
    Medical University-Sofia)

Abstract

Dominant mutations in tyrosyl-tRNA synthetase (YARS1) and six other tRNA ligases cause Charcot-Marie-Tooth peripheral neuropathy (CMT). Loss of aminoacylation is not required for their pathogenicity, suggesting a gain-of-function disease mechanism. By an unbiased genetic screen in Drosophila, we link YARS1 dysfunction to actin cytoskeleton organization. Biochemical studies uncover yet unknown actin-bundling property of YARS1 to be enhanced by a CMT mutation, leading to actin disorganization in the Drosophila nervous system, human SH-SY5Y neuroblastoma cells, and patient-derived fibroblasts. Genetic modulation of F-actin organization improves hallmark electrophysiological and morphological features in neurons of flies expressing CMT-causing YARS1 mutations. Similar beneficial effects are observed in flies expressing a neuropathy-causing glycyl-tRNA synthetase. Hence, in this work, we show that YARS1 is an evolutionary-conserved F-actin organizer which links the actin cytoskeleton to tRNA-synthetase-induced neurodegeneration.

Suggested Citation

  • Biljana Ermanoska & Bob Asselbergh & Laura Morant & Maria-Luise Petrovic-Erfurth & Seyyedmohsen Hosseinibarkooie & Ricardo Leitão-Gonçalves & Leonardo Almeida-Souza & Sven Bervoets & Litao Sun & LaTas, 2023. "Tyrosyl-tRNA synthetase has a noncanonical function in actin bundling," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35908-3
    DOI: 10.1038/s41467-023-35908-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-35908-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-35908-3?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. Sven Niehues & Julia Bussmann & Georg Steffes & Ines Erdmann & Caroline Köhrer & Litao Sun & Marina Wagner & Kerstin Schäfer & Guangxia Wang & Sophia N. Koerdt & Morgane Stum & Sumit Jaiswal & Uttam L, 2015. "Impaired protein translation in Drosophila models for Charcot–Marie–Tooth neuropathy caused by mutant tRNA synthetases," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    2. Lujia Zhou & Joseph McInnes & Keimpe Wierda & Matthew Holt & Abigail G. Herrmann & Rosemary J. Jackson & Yu-Chun Wang & Jef Swerts & Jelle Beyens & Katarzyna Miskiewicz & Sven Vilain & Ilse Dewachter , 2017. "Tau association with synaptic vesicles causes presynaptic dysfunction," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
    3. Sven Bervoets & Na Wei & Maria-Luise Erfurth & Shazie Yusein-Myashkova & Biljana Ermanoska & Ligia Mateiu & Bob Asselbergh & David Blocquel & Priyanka Kakad & Tyrone Penserga & Florian P Thomas & Veli, 2019. "Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    4. Weiwei He & Ge Bai & Huihao Zhou & Na Wei & Nicholas M. White & Janelle Lauer & Huaqing Liu & Yi Shi & Calin Dan Dumitru & Karen Lettieri & Veronica Shubayev & Albena Jordanova & Velina Guergueltcheva, 2015. "CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase," Nature, Nature, vol. 526(7575), pages 710-714, October.
    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. Noemi Gioelli & Lisa J. Neilson & Na Wei & Giulia Villari & Wenqian Chen & Bernhard Kuhle & Manuel Ehling & Federica Maione & Sander Willox & Serena Brundu & Daniele Avanzato & Grigorios Koulouras & M, 2022. "Neuropilin 1 and its inhibitory ligand mini-tryptophanyl-tRNA synthetase inversely regulate VE-cadherin turnover and vascular permeability," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Sukanta Jash & Sayani Banerjee & Shibin Cheng & Bin Wang & Chenxi Qiu & Asami Kondo & Jan Ernerudh & Xiao Zhen Zhou & Kun Ping Lu & Surendra Sharma, 2023. "Cis P-tau is a central circulating and placental etiologic driver and therapeutic target of preeclampsia," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Bob J. Ignacio & Jelmer Dijkstra & Natalia Mora & Erik F. J. Slot & Margot J. Weijsten & Erik Storkebaum & Michiel Vermeulen & Kimberly M. Bonger, 2023. "THRONCAT: metabolic labeling of newly synthesized proteins using a bioorthogonal threonine analog," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Salim Megat & Natalia Mora & Jason Sanogo & Olga Roman & Alberto Catanese & Najwa Ouali Alami & Axel Freischmidt & Xhuljana Mingaj & Hortense Calbiac & François Muratet & Sylvie Dirrig-Grosch & Stépha, 2023. "Integrative genetic analysis illuminates ALS heritability and identifies risk genes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Shanley F. Longfield & Mahdie Mollazade & Tristan P. Wallis & Rachel S. Gormal & Merja Joensuu & Jesse R. Wark & Ashley J. Waardenberg & Christopher Small & Mark E. Graham & Frédéric A. Meunier & Ramó, 2023. "Tau forms synaptic nano-biomolecular condensates controlling the dynamic clustering of recycling synaptic vesicles," Nature Communications, Nature, vol. 14(1), pages 1-20, 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_s41467-023-35908-3. 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.