IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v2y2011i1d10.1038_ncomms1161.html
   My bibliography  Save this article

Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor

Author

Listed:
  • Hiroshi Hanafusa

    (Graduate school of Science, Nagoya University, Chikusa-ku)

  • Kouki Ishikawa

    (Graduate school of Science, Nagoya University, Chikusa-ku)

  • Shin Kedashiro

    (Graduate school of Science, Nagoya University, Chikusa-ku)

  • Tsukasa Saigo

    (Graduate school of Science, Nagoya University, Chikusa-ku)

  • Shun-ichiro Iemura

    (National Institutes of Advanced Industrial Science and Technology, Biological Information Research Center (JBIRC), Kohtoh-ku)

  • Tohru Natsume

    (National Institutes of Advanced Industrial Science and Technology, Biological Information Research Center (JBIRC), Kohtoh-ku)

  • Masayuki Komada

    (Graduate school of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-16 Nagatsuta, Midori-ku)

  • Hiroshi Shibuya

    (Medical Research Institute, Tokyo Medical and Dental University, Chiyoda-ku)

  • Atsuki Nara

    (Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology)

  • Kunihiro Matsumoto

    (Graduate school of Science, Nagoya University, Chikusa-ku)

Abstract

Activation of the epidermal growth factor receptor (EGFR) not only initiates multiple signal-transduction pathways, including the MAP kinase (MAPK) pathway, but also triggers trafficking events that relocalize receptors from the cell surface to intracellular endocytic compartments. In this paper, we demonstrate that leucine-rich repeat kinase LRRK1, which contains a MAPKKK-like kinase domain, forms a complex with activated EGFR through an interaction with Grb2. Subsequently, LRRK1 and epidermal growth factor (EGF) are internalized and co-localized in early endosomes. LRRK1 regulates EGFR transport from early to late endosomes and regulates the motility of EGF-containing early endosomes in a manner dependent on its kinase activity. Furthermore, LRRK1 serves as a scaffold facilitating the interaction of EGFR with the endosomal sorting complex required for transport-0 complex, thus enabling efficient sorting of EGFR to the inner vesicles of multivesicular bodies. Our findings provide the first evidence that a MAPKKK-like protein regulates the endosomal trafficking of EGFR.

Suggested Citation

  • Hiroshi Hanafusa & Kouki Ishikawa & Shin Kedashiro & Tsukasa Saigo & Shun-ichiro Iemura & Tohru Natsume & Masayuki Komada & Hiroshi Shibuya & Atsuki Nara & Kunihiro Matsumoto, 2011. "Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor," Nature Communications, Nature, vol. 2(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1161
    DOI: 10.1038/ncomms1161
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms1161
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms1161?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. 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:2:y:2011:i:1:d:10.1038_ncomms1161. 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.