Leucine-rich repeat kinase 2 (LRRK2) is a key player in the pathogenesis of Parkinson's disease. Mutations in LRRK2 are associated with increased kinase activity that correlates with cytotoxicity, indicating that kinase inhibitors may comprise promising disease-modifying compounds. However, before embarking on such strategies, detailed knowledge of the cellular deficits mediated by pathogenic LRRK2 in the context of defined and pathologically relevant kinase substrates is essential. LRRK2 has been consistently shown to impair various intracellular vesicular trafficking events, and recent studies have shown that LRRK2 can phosphorylate a subset of proteins that are intricately implicated in those processes. In light of these findings, we here review the link between cellular deficits in intracellular trafficking pathways and the LRRK2-mediated phosphorylation of those newly identified substrates.
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February 2017
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Cover Image
Cover Image
The surface of the catalytic subunit of protein phosphatase PP1 (central 3D-structure) has many binding sites for regulatory proteins that are embedded in regulatory networks (coloured circles linked by lines). Please see pp. 89–99 for more information. Image provided by Mathieu Bollen.
Review Article|
February 15 2017
Cellular effects mediated by pathogenic LRRK2: homing in on Rab-mediated processes
Jesús Madero-Pérez;
Jesús Madero-Pérez
*
Institute of Parasitology and Biomedicine ‘López-Neyra’, Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain
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Elena Fdez;
Elena Fdez
*
Institute of Parasitology and Biomedicine ‘López-Neyra’, Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain
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Belén Fernández;
Belén Fernández
Institute of Parasitology and Biomedicine ‘López-Neyra’, Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain
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Antonio Jesús Lara Ordóñez;
Antonio Jesús Lara Ordóñez
Institute of Parasitology and Biomedicine ‘López-Neyra’, Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain
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Marian Blanca Ramírez;
Marian Blanca Ramírez
Institute of Parasitology and Biomedicine ‘López-Neyra’, Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain
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María Romo Lozano;
María Romo Lozano
Institute of Parasitology and Biomedicine ‘López-Neyra’, Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain
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Pilar Rivero-Ríos;
Pilar Rivero-Ríos
Institute of Parasitology and Biomedicine ‘López-Neyra’, Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain
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Sabine Hilfiker
Institute of Parasitology and Biomedicine ‘López-Neyra’, Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain
Correspondence: Sabine Hilfiker (sabine.hilfiker@ipb.csic.es)
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Publisher: Portland Press Ltd
Received:
September 16 2016
Revision Received:
November 04 2016
Accepted:
November 11 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2017
Biochem Soc Trans (2017) 45 (1): 147–154.
Article history
Received:
September 16 2016
Revision Received:
November 04 2016
Accepted:
November 11 2016
Citation
Jesús Madero-Pérez, Elena Fdez, Belén Fernández, Antonio Jesús Lara Ordóñez, Marian Blanca Ramírez, María Romo Lozano, Pilar Rivero-Ríos, Sabine Hilfiker; Cellular effects mediated by pathogenic LRRK2: homing in on Rab-mediated processes. Biochem Soc Trans 8 February 2017; 45 (1): 147–154. doi: https://doi.org/10.1042/BST20160392
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