ArticleScientific reports2016
LRRK2 and RAB7L1 coordinately regulate axonal morphology and lysosome integrity in diverse cellular contexts.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Associations of rs823128, rs1572931, and rs823156 polymorphisms with reduced Parkinson's disease risks.Neuroreport · 2017Pooled it
- Elucidating the molecular interplay between LRRK2 and Rab GTPases.bioRxiv : the preprint server for biology · 2026Article
- LRRK2 kinase mediates increased GCase activity in microglia in response to IFNγ-induced proinflammatory stimulation.NPJ Parkinson's disease · 2026Article
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- LRRK2 integrates Rab and GABARAP interactions to sense and respond to distinct lysosomal stresses.bioRxiv : the preprint server for biology · 2025Article
- Mitochondrial organization in the developing proximal tubule is controlled by LRRK2.Nature communications · 2025Article
- The Rab3 family proteins in age-related neurodegeneration: unraveling molecular pathways and potential therapeutic targets.npj aging · 2025Review
- The spectrum of lysosomal stress and damage responses: from mechanosensing to inflammation.EMBO reports · 2025Review
- Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects.Frontiers in cell and developmental biology · 2025Article
- Role of Dardarin and Isthmin-1 in the Protective Effect of Hydroxytyrosol Against Corn Syrup-Induced Liver Damage.Cureus · 2025Article
- Molecular regulation of axon termination in mechanosensory neurons.Development (Cambridge, England) · 2024Review
- Regulation of TIR-1/SARM-1 by miR-71 Protects Dopaminergic Neurons in aInternational journal of molecular sciences · 2024Article
- Article
- LRK-1/LRRK2 and AP-3 regulate trafficking of synaptic vesicle precursors through active zone protein SYD-2/Liprin-α.PLoS genetics · 2024Article
- UNC-16 interacts with LRK-1 and WDFY-3 to regulate the termination of axon growth.bioRxiv : the preprint server for biology · 2024Article
- Lysosomal stress drives the release of pathogenic α-synuclein from macrophage lineage cells via the LRRK2-Rab10 pathway.iScience · 2024Article
- Rab29-dependent asymmetrical activation of leucine-rich repeat kinase 2.Science (New York, N.Y.) · 2023Article
- Review
- Leucine-rich repeat kinase 2 at a glance.Journal of cell science · 2023Article
- Multiomics Data Analysis Identified CpG Sites That Mediate the Impact of Smoking on Cardiometabolic Traits.Epigenomes · 2023Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leucine-rich repeat kinase 2 (LRRK2) has been linked to several clinical disorders including Parkinson's disease (PD), Crohn's disease, and leprosy. Furthermore in rodents, LRRK2 deficiency or inhibition leads to lysosomal pathology in kidney and lung. Here we provide evidence that LRRK2 functions together with a second PD-associated gene, RAB7L1, within an evolutionarily conserved genetic module in diverse cellular contexts. In C. elegans neurons, orthologues of LRRK2 and RAB7L1 act coordinately in an ordered genetic pathway to regulate axonal elongation. Further genetic studies implicated the AP-3 complex, which is a known regulator of axonal morphology as well as of intracellular protein trafficking to the lysosome compartment, as a physiological downstream effector of LRRK2 and RAB7L1. Additional cell-based studies implicated LRRK2 in the AP-3 complex-related intracellular trafficking of lysosomal membrane proteins. In mice, deficiency of either RAB7L1 or LRRK2 leads to prominent age-associated lysosomal defects in kidney proximal tubule cells, in the absence of frank CNS pathology. We hypothesize that defects in this evolutionarily conserved genetic pathway underlie the diverse pathologies associated with LRRK2 in humans and in animal models.
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