ArticleThe EMBO journal2020
LRRK2 and Rab10 coordinate macropinocytosis to mediate immunological responses in phagocytes.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 102 citations in OpenAlex.
- Protocol to quantify LRRK2-mediated Rab10 phosphorylation using high-content imaging.STAR protocols · 2026Article
- The Parkinson's disease-linked G2019S mutation of LRRK2 increases NADPH oxidase-2 activity in neutrophils for superior control of bacterial infections.Cellular & molecular immunology · 2026Article
- Intracellular Localization of PD-L1 in Rab10-positive Open Tubular Endosome System of Cancer Cells.Acta histochemica et cytochemica · 2026Article
- Role of MEG3-miRNAs in immune-inflammatory regulation in age-dependent wool follicle remodeling in Tan sheep.BMC genomics · 2026Article
- Exosome RAB10 inhibits JAK1/STAT1 to hinder macrophage M1 polarization and promote tumor immune escape.Cell communication and signaling : CCS · 2026Article
- Lysosomal swelling triggers LRRK2 activity.bioRxiv : the preprint server for biology · 2025Article
- LRRK2 kinase-mediated accumulation of lysosome-associated phospho-Rabs in tauopathies and synucleinopathies.Acta neuropathologica · 2025Article
- Targeting specific kinase substrates rescues increased colitis severity induced by the Crohn's disease-linked LRRK2-N2081D variant.The Journal of clinical investigation · 2025Article
- Multiple interactions recruit BLTP2 to ER-PM contacts to control plasma membrane dynamics.The Journal of cell biology · 2025Article
- Macropinosomes are a site of HIV-1 entry into primary CD4Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Environmental Factors Exacerbate Parkinsonian Phenotypes in an Asian-Specific Knock-In LRRK2 Risk Variant in Mice.International journal of molecular sciences · 2025Article
- Salmonella exploits LRRK2-dependent plasma membrane dynamics to invade host cells.Nature communications · 2025Article
- Prognostic model of ubiquitination-related genes in ovarian cancer based on transcriptomic analysis and experimental validation.Frontiers in immunology · 2025Article
- The role of small GTPases in Alzheimer's disease tau pathologies.Frontiers in cellular neuroscience · 2025Review
- 14-3-3 phosphorylation inhibits 14-3-3θ's ability to regulate LRRK2 kinase activity and toxicity.Human molecular genetics · 2024Article
- PAK6 rescues pathogenic LRRK2-mediated ciliogenesis and centrosomal cohesion defects in a mutation-specific manner.Cell death & disease · 2024Article
- Cellular Regulation of Macropinocytosis.International journal of molecular sciences · 2024Review
- Single molecule array measures of LRRK2 kinase activity in serum link Parkinson's disease severity to peripheral inflammation.Molecular neurodegeneration · 2024Article
- Integrated drug profiling and CRISPR screening identify BCR::ABL1-independent vulnerabilities in chronic myeloid leukemia.Cell reports. Medicine · 2024Article
- Impairment of the Glial Phagolysosomal System Drives Prion-Like Propagation in aThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Genetic variation in LRRK2 associates with the susceptibility to Parkinson's disease, Crohn's disease, and mycobacteria infection. High expression of LRRK2 and its substrate Rab10 occurs in phagocytic cells in the immune system. In mouse and human primary macrophages, dendritic cells, and microglia-like cells, we find that Rab10 specifically regulates a specialized form of endocytosis known as macropinocytosis, without affecting phagocytosis or clathrin-mediated endocytosis. LRRK2 phosphorylates cytoplasmic PI(3,4,5)P3-positive GTP-Rab10, before EEA1 and Rab5 recruitment to early macropinosomes occurs. Macropinosome cargo in macrophages includes CCR5, CD11b, and MHCII, and LRRK2-phosphorylation of Rab10 potently blocks EHBP1L1-mediated recycling tubules and cargo turnover. EHBP1L1 overexpression competitively inhibits LRRK2-phosphorylation of Rab10, mimicking the effects of LRRK2 kinase inhibition in promoting cargo recycling. Both Rab10 knockdown and LRRK2 kinase inhibition potently suppress the maturation of macropinosome-derived CCR5-loaded signaling endosomes that are critical for CCL5-induced immunological responses that include Akt activation and chemotaxis. These data support a novel signaling axis in the endolysosomal system whereby LRRK2-mediated Rab10 phosphorylation stalls vesicle fast recycling to promote PI3K-Akt immunological responses.
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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.