IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms6827.html
   My bibliography  Save this article

Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering via differential interaction with ARHGEF7

Author

Listed:
  • Ruth Chia

    (Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging
    Present address: Department of Neuroscience, Biomarker Laboratory and Biorepository, Georgetown University Medical Centre, 3970 Reservoir Road, Washington, District of Colombia 20057, USA)

  • Sara Haddock

    (Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging)

  • Alexandra Beilina

    (Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging)

  • Iakov N. Rudenko

    (Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging)

  • Adamantios Mamais

    (Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging)

  • Alice Kaganovich

    (Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging)

  • Yan Li

    (Peptide Sequencing Facility, National Institute of Neurological Disorders and Stroke/NIH)

  • Ravindran Kumaran

    (Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging)

  • Michael A. Nalls

    (Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging)

  • Mark R. Cookson

    (Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging)

Abstract

LRRK2, a gene relevant to Parkinson's disease, encodes a scaffolding protein with both GTPase and kinase activities. LRRK2 protein is itself phosphorylated and therefore is subject to regulation by cell signalling; however, the kinase(s) responsible for this event have not been definitively identified. Here using an unbiased siRNA kinome screen, we identify and validate casein kinase 1α (CK1α) as being responsible for LRRK2 phosphorylation, including in the adult mouse striatum. We further show that LRRK2 recruitment to TGN46-positive Golgi-derived vesicles is modulated by constitutive LRRK2 phosphorylation by CK1α. These effects are mediated by differential protein interactions of LRRK2 with a guanine nucleotide exchange factor, ARHGEF7. These pathways are therefore likely involved in the physiological maintenance of the Golgi in cells, which may play a role in the pathogenesis of Parkinson’s disease.

Suggested Citation

  • Ruth Chia & Sara Haddock & Alexandra Beilina & Iakov N. Rudenko & Adamantios Mamais & Alice Kaganovich & Yan Li & Ravindran Kumaran & Michael A. Nalls & Mark R. Cookson, 2014. "Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering via differential interaction with ARHGEF7," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6827
    DOI: 10.1038/ncomms6827
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms6827
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms6827?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
    ---><---

    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_ncomms6827. 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.