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Sequential screening nominates the Parkinson's disease associated kinase LRRK2 as a regulator of Clathrin-mediated endocytosis

Authors
  • Heaton, George R.1, 2
  • Landeck, Natalie1
  • Mamais, Adamantios1
  • Nalls, Mike A.1, 3
  • Nixon-Abell, Jonathon4
  • Kumaran, Ravindran1
  • Beilina, Alexandra1
  • Pellegrini, Laura1
  • Li, Yan5
  • Harvey, Kirsten2
  • Cookson, Mark R.1
  • 1 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20814, USA
  • 2 Department of Pharmacology, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK
  • 3 Data Tecnica International, Glen Echo, MD, USA
  • 4 Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK
  • 5 Mass spectrometry Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 20814, USA
Type
Published Article
Journal
Neurobiology of Disease
Publisher
Elsevier
Publication Date
Jul 01, 2020
Volume
141
Identifiers
DOI: 10.1016/j.nbd.2020.104948
PMID: 32434048
PMCID: PMC7339134
Source
PubMed Central
Keywords
License
Unknown

Abstract

• LRRK2 interacts with components of the clathrin adaptor complex AP2. • LRRK2 KO animals exhibit a significant depletion of AP2 and Clathrin. • The LRRK2-R1441C pathogenic mutation reduces endocytosis in cellular models. • Clathrin-dependent endocytosis genes are associated with Parkinson's disease.

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