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Review
. 2018 Jul;373(1):39-50.
doi: 10.1007/s00441-017-2759-9. Epub 2018 Jan 8.

The LRRK2 signalling system

Alice Price  1 , Claudia Manzoni  1   2 , Mark R Cookson  3 , Patrick A Lewis  4   5
Affiliations
Review

The LRRK2 signalling system

Alice Price et al. Cell Tissue Res. 2018 Jul.

Abstract

The LRRK2 gene is a major contributor to genetic risk for Parkinson's disease and understanding the biology of the leucine-rich repeat kinase 2 (LRRK2, the protein product of this gene) is an important goal in Parkinson's research. LRRK2 is a multi-domain, multi-activity enzyme and has been implicated in a wide range of signalling events within the cell. Because of the complexities of the signal transduction pathways in which LRRK2 is involved, it has been challenging to generate a clear idea as to how mutations and disease associated variants in this gene are altered in disease. Understanding the events in which LRRK2 is involved at a systems level is therefore critical to fully understand the biology and pathobiology of this protein and is the subject of this review.

Keywords: Kinase; LRRK2; Parkinson’s disease; ROCO protein; Signal transduction.

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Figures

Fig. 1
Fig. 1
Disease-associated coding variants in LRRK2. Penetrant mutations associated with Parkinson’s disease are displayed in red, protective variants in green and disease-associated risk variants in blue
Fig. 2
Fig. 2
Phospho-events regulating LRRK2. Autophosphorylation is shown in purple, phosphorylation events mediated by another kinase in blue
Fig. 3
Fig. 3
An example of a simplified regulatory network for LRRK2 signalling biology, showing phosphorylation events and protein/protein interactions
See this image and copyright information in PMC

References

    1. Agalliu I, San Luciano M, Mirelman A, Giladi N, Waro B, Aasly J, Inzelberg R, Hassin-Baer S, Friedman E, Ruiz-Martinez J, Marti-Masso JF, Orr-Urtreger A, Bressman S, Saunders-Pullman R. Higher frequency of certain cancers in LRRK2 G2019S mutation carriers with Parkinson disease: a pooled analysis. JAMA Neurol. 2015;72(1):58–65. doi: 10.1001/jamaneurol.2014.1973. - DOI - PMC - PubMed
    1. Alegre-Abarrategui J, Christian H, Lufino MMP, Mutihac R, Venda LL, Ansorge O, Wade-Martins R. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum Mol Genet. 2009;18(21):4022–4034. doi: 10.1093/hmg/ddp346. - DOI - PMC - PubMed
    1. Atashrazm F, Dzamko N (2016) LRRK2 inhibitors and their potential in the treatment of Parkinson’s disease. Curr Perspect Clin Pharmacol Adv Applic 8:177–189. doi: 10.2147/CPAA.S102191 - PMC - PubMed
    1. Aylett CHS, Sauer E, Imseng S, Boehringer D, Hall MN, Ban N, Maier T. Architecture of human mTOR complex 1. Science. 2016;351(6268):48–52. doi: 10.1126/science.aaa3870. - DOI - PubMed
    1. Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS, Taylor KD, Barmada MM, Bitton A, Dassopoulos T, Datta LW, Green T, Griffiths AM, Kistner EO, Murtha MT, Regueiro MD, Rotter JI, Schumm LP, Steinhart AH, Targan SR, Xavier RJ, NIDDK IBD Genetics Consortium. Libioulle C, Sandor C, Lathrop M, Belaiche J, Dewit O, Gut I, Heath S, Laukens D, Mni M, Rutgeerts P, Van Gossum A, Zelenika D, Franchimont D, Hugot J-P, de Vos M, Vermeire S, Louis E, Belgian-French IBD Consortium. Wellcome Trust Case Control Consortium. Cardon LR, Anderson CA, Drummond H, Nimmo E, Ahmad T, Prescott NJ, Onnie CM, Fisher SA, Marchini J, Ghori J, Bumpstead S, Gwilliam R, Tremelling M, Deloukas P, Mansfield J, Jewell D, Satsangi J, Mathew CG, Parkes M, Georges M, Daly MJ. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet. 2008;40(8):955–962. doi: 10.1038/ng.175. - DOI - PMC - PubMed

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