ArticleScience advances2020
LRRK2 mediates tubulation and vesicle sorting from lysosomes.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 4 of them syntheses that pooled it.
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Who cites it
178 citing papers in PubMed, 4 syntheses or guidelines pooled it, 271 citations in OpenAlex.
- Omics research in Parkinson's disease: evolution, integrated analysis, pathogenic mechanisms, biomarkers, and therapeutic targets.Frontiers in molecular neuroscience · 2026Pooled it
- Multi-ancestry genome-wide association meta-analysis of Parkinson's disease.Nature genetics · 2024Pooled it
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- Coding and Noncoding Variation in LRRK2 and Parkinson's Disease Risk.Movement disorders : official journal of the Movement Disorder Society · 2022Pooled it
- ClC-7 links PIKfyve inhibition to Rab-dependent LRRK2 activity at lysosomes.The Journal of cell biology · 2026Article
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- CRISPR screening in neurodegeneration and lysosomal biology: Uncovering disease mechanisms and genetic modifiers.Molecular genetics and metabolism · 2026Review
- Subtype-specific secretion of extracellular vesicles by LRRK2 and Rab GTPases under lysosomal stress.iScience · 2026Article
- Mitochondrial Quality Control Imbalance in the Heterogeneity of Parkinson's Disease: From Selective Vulnerability to Stratified Transformation.International journal of molecular sciences · 2026Review
- Parkinson's disease-associated LRRK2 risk variant, G2385R, enhances Rab substrate phosphorylation and impairs neuronal integrity.Human molecular genetics · 2026Article
- Protocol to quantify LRRK2-mediated Rab10 phosphorylation using high-content imaging.STAR protocols · 2026Article
- LRRK2: Molecular Mechanisms in Parkinson's Disease.International journal of molecular sciences · 2026Review
- Astrocytes mobilize a broader repertoire of lysosomal repair mechanisms than neurons.iScience · 2026Article
- Lysosomal channel TPC2 modulates microglia-endothelial signaling in choroidal angiogenesis.Angiogenesis · 2026Article
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- Parkinson's disease LRRK2 mutations dysregulate iron homeostasis and promote oxidative stress and ferroptosis in human neurons and astrocytes.Molecular neurodegeneration · 2026Article
- Lysophagy protects against ANXA11 amyloid fibril toxicity and propagation in FTLD.Translational neurodegeneration · 2026Article
- Knockout of the LRRK2-counteracting RAB phosphatase PPM1H disrupts axonal autophagy and exacerbates alpha-synuclein aggregation.Cell reports · 2026Article
- Review
- Proximity proteomics reveals a co-evolved LRRK2-regulatory network linked to centrosomes.EMBO reports · 2026Article
118 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic variation around the LRRK2 gene affects risk of both familial and sporadic Parkinson's disease (PD). However, the biological functions of LRRK2 remain incompletely understood. Here, we report that LRRK2 is recruited to lysosomes after exposure of cells to the lysosome membrane-rupturing agent LLOME. Using an unbiased proteomic screen, we identified the motor adaptor protein JIP4 as an LRRK2 partner at the lysosomal membrane. LRRK2 can recruit JIP4 to lysosomes in a kinase-dependent manner via the phosphorylation of RAB35 and RAB10. Using super-resolution live-cell imaging microscopy and FIB-SEM, we demonstrate that JIP4 promotes the formation of LAMP1-negative tubules that release membranous content from lysosomes. Thus, we describe a new process orchestrated by LRRK2, which we name LYTL (LYsosomal Tubulation/sorting driven by LRRK2), by which lysosomal tubulation is used to release vesicles from lysosomes. Given the central role of the lysosome in PD, LYTL is likely to be disease relevant.
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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.