ArticleAmerican journal of physiology. Renal physiology2018
LRRK2 deficiency impairs trans-Golgi to lysosome trafficking and endocytic cargo degradation in human renal proximal tubule epithelial cells.
Article in American journal of physiology. Renal physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Interruption of Endolysosomal Trafficking After Focal Brain Ischemia.Frontiers in molecular neuroscience · 2021Pooled it
- Leucine-rich repeat kinase 2 (LRRK2): balancing cellular homeostasis and Parkinson's disease (PD) pathogenesis.Annals of medicine · 2026Review
- Hydroxytyrosol has a protective effect on the kidneys through dardarin and spexin.Northern clinics of Istanbul · 2025Article
- Impairment of the trans-Golgi-Lysosomal Pathway Accelerates Dopaminergic Neuronal Senescence in LRRK2Aging and disease · 2024Article
- LRK-1/LRRK2 and AP-3 regulate trafficking of synaptic vesicle precursors through active zone protein SYD-2/Liprin-α.PLoS genetics · 2024Article
- The function of Golgi apparatus in LRRK2-associated Parkinson's disease.Frontiers in molecular neuroscience · 2023Review
- Lysosomal Pathogenesis of Parkinson's Disease: Insights From LRRK2 and GBA1 Rodent Models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- LRRK2 regulates actin assembly for spindle migration and mitochondrial function in mouse oocyte meiosis.Journal of molecular cell biology · 2022Article
- Mutations in LRRK2 linked to Parkinson disease sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia.PLoS biology · 2021Article
- LRRK2 along the Golgi and lysosome connection: a jamming situation.Biochemical Society transactions · 2021Review
- Inhibiting PKCβ2 protects HK-2 cells against meglumine diatrizoate and AGEs-induced apoptosis and autophagy.Annals of translational medicine · 2020Article
- The tripartite interaction of phosphate, autophagy, and αKlotho in health maintenance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- LRRK2 and the Endolysosomal System in Parkinson's Disease.Journal of Parkinson's disease · 2020Review
- Lysosomal Dysfunction at the Centre of Parkinson's Disease and Frontotemporal Dementia/Amyotrophic Lateral Sclerosis.Trends in neurosciences · 2019Review
- LRRK2 links genetic and sporadic Parkinson's disease.Biochemical Society transactions · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Defects in vesicular trafficking underlie a wide variety of human diseases. Genetic disruption of leucine-rich repeat kinase 2 (LRRK2) in rodents results in epithelial vesicular trafficking errors that can also be induced by treatment of animals with LRRK2 kinase inhibitors. Here we demonstrate that defects in human renal cells lacking LRRK2 phenocopy those seen in the kidneys of Lrrk2 knockout mice, characterized by accumulation of intracellular waste vesicles and fragmentation of the Golgi apparatus. This phenotype can be recapitulated by knockdown of N-ethylmaleimide-sensitive factor, which physically associates with LRRK2 in renal cells. Deficiency in either protein leads to a defect in trans-Golgi to lysosome protein trafficking, which compromises the capacity of lysosomes to degrade endocytic and autophagic cargo. In contrast, neither bulk endocytosis nor autophagic flux are impaired when LRRK2 is acutely knocked down in normal immortalized human kidney (HK2) cells. These data collectively suggest that the primary renal defect caused by LRRK2 deficiency is in protein trafficking between the Golgi apparatus and late endosome/lysosome, which leads to progressive impairments in lysosomal function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.