title: Cellular effects mediated by pathogenic LRRK2: homing in on Rab-mediated processes.
abstract: 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.
authors.affiliation: Institute of Parasitology and Biomedicine 'López-Neyra', Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Madero-Pérez
authors.affiliation: Institute of Parasitology and Biomedicine 'López-Neyra', Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Fdez
authors.affiliation: Institute of Parasitology and Biomedicine 'López-Neyra', Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Fernández
authors.affiliation: Institute of Parasitology and Biomedicine 'López-Neyra', Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain.
authors.forename: Antonio Jesús
authors.initials: AJ
authors.lastname: Lara Ordóñez
authors.affiliation: Institute of Parasitology and Biomedicine 'López-Neyra', Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain.
authors.forename: Marian
authors.initials: M
authors.lastname: Blanca Ramírez
authors.affiliation: Institute of Parasitology and Biomedicine 'López-Neyra', Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Romo Lozano
authors.affiliation: Institute of Parasitology and Biomedicine 'López-Neyra', Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Rivero-Ríos
authors.affiliation: Institute of Parasitology and Biomedicine 'López-Neyra', Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain sabine.hilfiker@ipb.csic.es.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hilfiker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D022161:Transport Vesicles / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D020691:rab GTP-Binding Proteins
keywords: GDI; GEF; REP; Rab protein; leucine-rich repeat kinase; vesicular trafficking