IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms5241.html
   My bibliography  Save this article

Rag GTPases are cardioprotective by regulating lysosomal function

Author

Listed:
  • Young Chul Kim

    (University of California at San Diego)

  • Hyun Woo Park

    (University of California at San Diego)

  • Sebastiano Sciarretta

    (Cardiovascular Research Institute, Rutgers New Jersey Medical School
    IRCCS Neuromed)

  • Jung-Soon Mo

    (University of California at San Diego)

  • Jenna L. Jewell

    (University of California at San Diego)

  • Ryan C. Russell

    (University of California at San Diego)

  • Xiaohui Wu

    (Institute of Developmental Biology and Molecular Medicine, Fudan University)

  • Junichi Sadoshima

    (Cardiovascular Research Institute, Rutgers New Jersey Medical School)

  • Kun-Liang Guan

    (University of California at San Diego)

Abstract

The Rag family proteins are Ras-like small GTPases that have a critical role in amino-acid-stimulated mTORC1 activation by recruiting mTORC1 to lysosome. Despite progress in the mechanistic understanding of Rag GTPases in mTORC1 activation, little is known about the physiological function of Rag GTPases in vivo. Here we show that loss of RagA and RagB (RagA/B) in cardiomyocytes results in hypertrophic cardiomyopathy and phenocopies lysosomal storage diseases, although mTORC1 activity is not substantially impaired in vivo. We demonstrate that despite upregulation of lysosomal protein expression by constitutive activation of the transcription factor EB (TFEB) in RagA/B knockout mouse embryonic fibroblasts, lysosomal acidification is compromised owing to decreased v-ATPase level in the lysosome fraction. Our study uncovers RagA/B GTPases as key regulators of lysosomal function and cardiac protection.

Suggested Citation

  • Young Chul Kim & Hyun Woo Park & Sebastiano Sciarretta & Jung-Soon Mo & Jenna L. Jewell & Ryan C. Russell & Xiaohui Wu & Junichi Sadoshima & Kun-Liang Guan, 2014. "Rag GTPases are cardioprotective by regulating lysosomal function," Nature Communications, Nature, vol. 5(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5241
    DOI: 10.1038/ncomms5241
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms5241
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms5241?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
    ---><---

    Citations

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


    Cited by:

    1. Kaushal Asrani & Juhyung Woo & Adrianna A. Mendes & Ethan Schaffer & Thiago Vidotto & Clarence Rachel Villanueva & Kewen Feng & Lia Oliveira & Sanjana Murali & Hans B. Liu & Daniela C. Salles & Brando, 2022. "An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss," Nature Communications, Nature, vol. 13(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:5:y:2014:i:1:d:10.1038_ncomms5241. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.