The LRRK2 signalling system

被引：30

作者：

Price, Alice ^{[1
]}

Manzoni, Claudia ^{[1
,2
]}

Cookson, Mark R. ^{[3
]}

Lewis, Patrick A. ^{[1
,2
]}

机构：

[1] Univ Reading, Sch Pharm, Reading RG6 6AP, Berks, England

[2] UCL Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England

[3] NIA, Lab Neurogenet, NIH, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA

来源：

CELL AND TISSUE RESEARCH | 2018年 / 373卷 / 01期

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

LRRK2; Signal transduction; Parkinson's disease; ROCO protein; Kinase; PARKINSONS-DISEASE; G2019S MUTATION; 14-3-3; BINDING; KINASE LRRK2; REPEAT; PHOSPHORYLATION; ASSOCIATION; GENE; ARCHITECTURE; INHIBITION;

D O I：

10.1007/s00441-017-2759-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：39 / 50

页数：12

共 84 条

[1] Higher Frequency of Certain Cancers in LRRK2 G2019S Mutation Carriers With Parkinson Disease A Pooled Analysis [J].

Agalliu, Ilir ;

San Luciano, Marta ;

Mirelman, Anat ;

Giladi, Nir ;

Waro, Bjorg ;

Aasly, Jan ;

Inzelberg, Rivka ;

Hassin-Baer, Sharon ;

Friedman, Eitan ;

Ruiz-Martinez, Javier ;

Felix Marti-Masso, Jose ;

Orr-Urtreger, Avi ;

Bressman, Susan ;

Saunders-Pullman, Rachel .

JAMA NEUROLOGY, 2015, 72 (01) :58-65

[2] LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model [J].

Alegre-Abarrategui, Javier ;

Christian, Helen ;

Lufino, Michele M. P. ;

Mutihac, Ruxandra ;

Venda, Lara Lourenco ;

Ansorge, Olaf ;

Wade-Martins, Richard .

HUMAN MOLECULAR GENETICS, 2009, 18 (21) :4022-4034

[3] LRRK2 inhibitors and their potential in the treatment of Parkinson's disease: current perspectives [J].

Atashrazm, Farzaneh ;

Dzamko, Nicolas .

CLINICAL PHARMACOLOGY-ADVANCES AND APPLICATIONS, 2016, 8 :177-189

[4] STRUCTURAL BIOLOGY Architecture of human mTOR complex 1 [J].

Aylett, Christopher H. S. ;

Sauer, Evelyn ;

Imseng, Stefan ;

Boehringer, Daniel ;

Hall, Michael N. ;

Ban, Nenad ;

Maier, Timm .

SCIENCE, 2016, 351 (6268) :48-52

[5] Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].

Barrett, Jeffrey C. ;

Hansoul, Sarah ;

Nicolae, Dan L. ;

Cho, Judy H. ;

Duerr, Richard H. ;

Rioux, John D. ;

Brant, Steven R. ;

Silverberg, Mark S. ;

Taylor, Kent D. ;

Barmada, M. Michael ;

Bitton, Alain ;

Dassopoulos, Themistocles ;

Datta, Lisa Wu ;

Green, Todd ;

Griffiths, Anne M. ;

Kistner, Emily O. ;

Murtha, Michael T. ;

Regueiro, Miguel D. ;

Rotter, Jerome I. ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Targan, Stephan R. ;

Xavier, Ramnik J. ;

Libioulle, Cecile ;

Sandor, Cynthia ;

Lathrop, Mark ;

Belaiche, Jacques ;

Dewit, Olivier ;

Gut, Ivo ;

Heath, Simon ;

Laukens, Debby ;

Mni, Myriam ;

Rutgeerts, Paul ;

Van Gossum, Andre ;

Zelenika, Diana ;

Franchimont, Denis ;

Hugot, Jean-Pierre ;

de Vos, Martine ;

Vermeire, Severine ;

Louis, Edouard ;

Cardon, Lon R. ;

Anderson, Carl A. ;

Drummond, Hazel ;

Nimmo, Elaine ;

Ahmad, Tariq ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Fisher, Sheila A. ;

Marchini, Jonathan ;

Ghori, Jilur .

NATURE GENETICS, 2008, 40 (08) :955-962

[6] Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease [J].

Beilina, Alexandria ;

Rudenko, Iakov N. ;

Kaganovich, Alice ;

Civiero, Laura ;

Chau, Hien ;

Kalia, Suneil K. ;

Kalia, Lorraine V. ;

Lobbestael, Evy ;

Chi, Ruth ;

Ndukwe, Kelechi ;

Ding, Jinhui ;

Nalls, Mike A. ;

Olszewski, Maciej ;

Hauser, David N. ;

Kumaran, Ravindran ;

Lozano, Andres M. ;

Baekelandt, Veerle ;

Greene, Lois E. ;

Taymans, Jean-Marc ;

Greggio, Elisa ;

Cookson, Mark R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (07) :2626-2631

[7] Membrane Localization of LRRK2 Is Associated with Increased Formation of the Highly Active LRRK2 Dimer and Changes in Its Phosphorylation [J].

Berger, Zdenek ;

Smith, Kelsey A. ;

LaVoie, Matthew J. .

BIOCHEMISTRY, 2010, 49 (26) :5511-5523

[8] LRRK2 signaling pathways: the key to unlocking neurodegeneration? [J].

Berwick, Daniell C. ;

Harvey, Kirsten .

TRENDS IN CELL BIOLOGY, 2011, 21 (05) :257-265

[9] Localization of LRRK2 to membranous and vesicular structures in mammalian brain [J].

Biskup, Saskia ;

Moore, Darren J. ;

Celsi, Fulvio ;

Higashi, Shinji ;

West, Andrew B. ;

Andrabi, Shaida A. ;

Kurkinen, Kaisa ;

Yu, Seong-Woon ;

Savitt, Joseph M. ;

Waldvogel, Henry J. ;

Faull, Richard L. M. ;

Emson, Piers C. ;

Torp, Reldun ;

Ottersen, Ole P. ;

Dawson, Ted M. ;

Dawson, Valina L. .

ANNALS OF NEUROLOGY, 2006, 60 (05) :557-569

[10] A comprehensive map of the mTOR signaling network [J].

Caron, Etienne ;

Ghosh, Samik ;

Matsuoka, Yukiko ;

Ashton-Beaucage, Dariel ;

Therrien, Marc ;

Lemieux, Sebastien ;

Perreault, Claude ;

Roux, Philippe P. ;

Kitano, Hiroaki .

MOLECULAR SYSTEMS BIOLOGY, 2010, 6

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