The Emerging Functions of LRRK2 and Rab GTPases in the Endolysosomal System

The G2019S variant of leucine-rich repeat kinase 2 (LRRK2) alters endolysosomal trafficking by impairing the function of the GTPase RAB8A

(2019) Pilar Rivero-Ríos et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

LRRK2 mutations impair depolarization-induced mitophagy through inhibition of mitochondrial accumulation of RAB10

(2019) Fieke Wauters et al.   Autophagy

Parkinson's disease age at onset genome‐wide association study: Defining heritability, genetic loci, and α‐synuclein mechanisms

(2019) Cornelis Blauwendraat et al.   MOVEMENT DISORDERS

Role of the endolysosomal system in Parkinson’s disease

(2019) D. J. Vidyadhara et al.   JOURNAL OF NEUROCHEMISTRY

RAB8, RAB10 and RILPL1 contribute to both LRRK2 kinase-mediated centrosomal cohesion and ciliogenesis deficits

(2019) Antonio Jesús Lara Ordóñez et al.   HUMAN MOLECULAR GENETICS

Higher Urine bis(Monoacylglycerol)Phosphate Levels in LRRK2 G2019S Mutation Carriers: Implications for Therapeutic Development

(2019) Roy N. Alcalay et al.   MOVEMENT DISORDERS

Lrrk2 alleles modulate inflammation during microbial infection of mice in a sex-dependent manner

(2019) Bojan Shutinoski et al.   Science Translational Medicine

Membrane association but not identity is required for LRRK2 activation and phosphorylation of Rab GTPases

(2019) Rachel C. Gomez et al.   JOURNAL OF CELL BIOLOGY

Parkinson's disease-associated mutant LRRK2 phosphorylates Rab7L1 and modifies trans-Golgi morphology

(2018) Tetta Fujimoto et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

The Parkinson's disease VPS35[D620N] mutation enhances LRRK2-mediated Rab protein phosphorylation in mouse and human

(2018) Rafeeq Mir et al.   BIOCHEMICAL JOURNAL

LRRK2 is a negative regulator of Mycobacterium tuberculosis phagosome maturation in macrophages

(2018) Anetta Härtlova et al.   EMBO JOURNAL

LRRK2 mediated Rab8a phosphorylation promotes lipid storage

(2018) Miao Yu et al.   Lipids in Health and Disease

Parkinson disease-associated mutations in LRRK2 cause centrosomal defects via Rab8a phosphorylation

(2018) Jesús Madero-Pérez et al.   Molecular Neurodegeneration

Dysregulated phosphorylation of Rab GTPases by LRRK2 induces neurodegeneration

(2018) Ga Ram Jeong et al.   Molecular Neurodegeneration

Familial knockin mutation of LRRK2 causes lysosomal dysfunction and accumulation of endogenous insoluble α-synuclein in neurons

(2018) Jason Schapansky et al.   NEUROBIOLOGY OF DISEASE

Regulation of myeloid cell phagocytosis by LRRK2 via WAVE2 complex stabilization is altered in Parkinson’s disease

(2018) Kwang Soo Kim et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Functional variants in the LRRK2 gene confer shared effects on risk for Crohn’s disease and Parkinson’s disease

(2018) Ken Y. Hui et al.   Science Translational Medicine

LRRK2 and its substrate Rab GTPases are sequentially targeted onto stressed lysosomes and maintain their homeostasis

(2018) Tomoya Eguchi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

LRRK2 activation in idiopathic Parkinson’s disease

(2018) Roberto Di Maio et al.   Science Translational Medicine

LRRK2 kinase regulates α-synuclein propagation via RAB35 phosphorylation

(2018) Eun-Jin Bae et al.   Nature Communications

The lysosome as a cellular centre for signalling, metabolism and quality control

(2018) Rosalie E. Lawrence et al.   NATURE CELL BIOLOGY

A pathway for Parkinson’s Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain

(2018) Herschel S Dhekne et al.   eLife

RAB7L1-Mediated Relocalization of LRRK2 to the Golgi Complex Causes Centrosomal Deficits via RAB8A

(2018) Jesús Madero-Pérez et al.   Frontiers in Molecular Neuroscience

LRRK2 phosphorylates membrane-bound Rabs and is activated by GTP-bound Rab7L1 to promote recruitment to the trans-Golgi network

(2017) Zhiyong Liu et al.   HUMAN MOLECULAR GENETICS

LRRK2 promotes the activation of NLRC4 inflammasome duringSalmonellaTyphimurium infection

(2017) Weiwei Liu et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Rab GTPases: master regulators that establish the secretory and endocytic pathways

(2017) Suzanne R. Pfeffer   MOLECULAR BIOLOGY OF THE CELL

A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci

(2017) Diana Chang et al.   NATURE GENETICS

Autophagy-related gene LRRK2 is likely a susceptibility gene for systemic lupus erythematosus in northern Han Chinese

(2017) Yue-miao Zhang et al.   Oncotarget

Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis

(2017) Martin Steger et al.   eLife

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

(2017) Genta Ito et al.   Jove-Journal of Visualized Experiments

Selective LRRK2 kinase inhibition reduces phosphorylation of endogenous Rab10 and Rab12 in human peripheral mononuclear blood cells

(2017) Kenneth Thirstrup et al.   Scientific Reports

Phos-tag analysis of Rab10 phosphorylation by LRRK2: a powerful assay for assessing kinase function and inhibitors

(2016) G. Ito et al.   BIOCHEMICAL JOURNAL

Mechanisms and functions of lysosome positioning

(2016) Jing Pu et al.   JOURNAL OF CELL SCIENCE

Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease

(2016) Kyle B. Fraser et al.   MOVEMENT DISORDERS

Increased Rab35 expression is a potential biomarker and implicated in the pathogenesis of Parkinson’s disease

(2016) Ching-Chi Chiu et al.   Oncotarget

Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases

(2016) Martin Steger et al.   eLife

LRRK2 and RAB7L1 coordinately regulate axonal morphology and lysosome integrity in diverse cellular contexts

(2016) Tomoki Kuwahara et al.   Scientific Reports

Leucine-rich repeat kinase 2 deficiency is protective in rhabdomyolysis-induced kidney injury

(2015) R. Boddu et al.   HUMAN MOLECULAR GENETICS

Pathogenic LRRK2 mutations, through increased kinase activity, produce enlarged lysosomes with reduced degradative capacity and increase ATP13A2 expression

(2015) Anastasia G. Henry et al.   HUMAN MOLECULAR GENETICS

Fine mapping and resequencing of the PARK16 locus in Parkinson’s disease

(2015) Lasse Pihlstrøm et al.   JOURNAL OF HUMAN GENETICS

Commensal bacteria direct selective cargo sorting to promote symbiosis

(2015) Qin Zhang et al.   NATURE IMMUNOLOGY

Effect of selective LRRK2 kinase inhibition on nonhuman primate lung

(2015) Reina N. Fuji et al.   Science Translational Medicine

Clinical Correlations With Lewy Body Pathology inLRRK2-Related Parkinson Disease

(2015) Lorraine V. Kalia et al.   JAMA Neurology

Ribosomal Protein s15 Phosphorylation Mediates LRRK2 Neurodegeneration in Parkinson’s Disease

(2014) Ian Martin et al.   CELL

Novel ethyl methanesulfonate (EMS)-induced null alleles of the Drosophila homolog of LRRK2 reveal a crucial role in endolysosomal functions and autophagy in vivo

(2014) M. W. Dodson et al.   Disease Models & Mechanisms

Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy

(2014) J. Schapansky et al.   HUMAN MOLECULAR GENETICS

LRRK2 delays degradative receptor trafficking by impeding late endosomal budding through decreasing Rab7 activity

(2014) Patricia Gómez-Suaga et al.   HUMAN MOLECULAR GENETICS

Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition

(2014) L. N. Hockey et al.   JOURNAL OF CELL SCIENCE

Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

(2014) Mike A Nalls et al.   NATURE GENETICS

A Role of Rab29 in the Integrity of the Trans-Golgi Network and Retrograde Trafficking of Mannose-6-Phosphate Receptor

(2014) Shicong Wang et al.   PLoS One

LIMP-2 expression is critical for  -glucocerebrosidase activity and  -synuclein clearance

(2014) M. Rothaug et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

(2014) A. Beilina et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Inhibition of LRRK2 kinase activity stimulates macroautophagy

(2013) Claudia Manzoni et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

The role ofSCARB2as susceptibility factor in Parkinson's disease

(2013) Franziska Hopfner et al.   MOVEMENT DISORDERS

Interplay of LRRK2 with chaperone-mediated autophagy

(2013) Samantha J Orenstein et al.   NATURE NEUROSCIENCE

RAB7L1 Interacts with LRRK2 to Modify Intraneuronal Protein Sorting and Parkinson’s Disease Risk

(2013) David A. MacLeod et al.   NEURON

Leucine-Rich Repeat Kinase 2 (LRRK2)-Deficient Rats Exhibit Renal Tubule Injury and Perturbations in Metabolic and Immunological Homeostasis

(2013) Daniel Ness et al.   PLoS One

Loss of Leucine-Rich Repeat Kinase 2 (LRRK2) in Rats Leads to Progressive Abnormal Phenotypes in Peripheral Organs

(2013) Marco A. S. Baptista et al.   PLoS One

LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors

(2012) Kelly M Hinkle et al.   Molecular Neurodegeneration

Loss of leucine-rich repeat kinase 2 causes age-dependent bi-phasic alterations of the autophagy pathway

(2012) Youren Tong et al.   Molecular Neurodegeneration

Evidence of an association between the scavenger receptor class B member 2 gene and Parkinson's disease

(2012) Helen Michelakakis et al.   MOVEMENT DISORDERS

LRRK2 Controls an EndoA Phosphorylation Cycle in Synaptic Endocytosis

(2012) Samer Matta et al.   NEURON

Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database

(2012) Christina M. Lill et al.   PLoS Genetics

A Mutation in VPS35, Encoding a Subunit of the Retromer Complex, Causes Late-Onset Parkinson Disease

(2011) Alexander Zimprich et al.   AMERICAN JOURNAL OF HUMAN GENETICS

VPS35 Mutations in Parkinson Disease

(2011) Carles Vilariño-Güell et al.   AMERICAN JOURNAL OF HUMAN GENETICS

LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice

(2011) Martin C. Herzig et al.   HUMAN MOLECULAR GENETICS

Roles of the Drosophila LRRK2 homolog in Rab7-dependent lysosomal positioning

(2011) M. W. Dodson et al.   HUMAN MOLECULAR GENETICS

Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP

(2011) Patricia Gómez-Suaga et al.   HUMAN MOLECULAR GENETICS

Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease

(2011) Chuong B. Do et al.   PLoS Genetics

Age-dependent and cell-population-restricted LRRK2 expression in normal mouse spleen

(2010) Tatsunori Maekawa et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Membrane Localization of LRRK2 Is Associated with Increased Formation of the Highly Active LRRK2 Dimer and Changes in Its Phosphorylation

(2010) Zdenek Berger et al.   BIOCHEMISTRY

LRRK2 Is Involved in the IFN-  Response and Host Response to Pathogens

(2010) A. Gardet et al.   JOURNAL OF IMMUNOLOGY

Leucine-Rich Repeat Kinase 2 Is Associated With the Endoplasmic Reticulum in Dopaminergic Neurons and Accumulates in the Core of Lewy Bodies in Parkinson Disease

(2010) Jérémie Vitte et al.   JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY

Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of  -synuclein, and apoptotic cell death in aged mice

(2010) Y. Tong et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model

(2009) Javier Alegre-Abarrategui et al.   HUMAN MOLECULAR GENETICS

Abnormal Localization of Leucine-Rich Repeat Kinase 2 to the Endosomal-Lysosomal Compartment in Lewy Body Disease

(2009) Shinji Higashi et al.   JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY

Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease

(2009) Wataru Satake et al.   NATURE GENETICS

Genome-wide association study reveals genetic risk underlying Parkinson's disease

(2009) Javier Simón-Sánchez et al.   NATURE GENETICS

Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function

(2009) Paul Saftig et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Genomewide Association Study of Leprosy

(2009) Fu-Ren Zhang et al.   NEW ENGLAND JOURNAL OF MEDICINE

Inclusion formation and neuronal cell death through neuron-to-neuron transmission of  -synuclein

(2009) P. Desplats et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells

(2008) Edward D. Plowey et al.   JOURNAL OF NEUROCHEMISTRY

Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease

(2008) Jeffrey C Barrett et al.   NATURE GENETICS