ArticleMolecular & cellular proteomics : MCP2011
A QUICK screen for Lrrk2 interaction partners--leucine-rich repeat kinase 2 is involved in actin cytoskeleton dynamics.
Article in Molecular & cellular proteomics : MCP, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 130 citations in OpenAlex.
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Article
- Proximity proteomics reveals a co-evolved LRRK2-regulatory network linked to centrosomes.EMBO reports · 2026Article
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- The E193K LRRK2 mutation interferes with the autophagosome processing through the impairment of the LRRK2-Dynein-1 complex.Scientific reports · 2025Article
- LRRK2 and the fragile synapse: a molecular prelude to Parkinson's disease?The Biochemical journal · 2025Review
- Loss of LRRK2 activity induces cytoskeleton defects and oxidative stress during porcine oocyte maturation.Cell communication and signaling : CCS · 2025Article
- RAB3 phosphorylation by pathogenic LRRK2 impairs trafficking of synaptic vesicle precursors.The Journal of cell biology · 2024Article
- How Parkinson's Disease-Linked LRRK2 Mutations Affect Different CNS Cell Types.Journal of Parkinson's disease · 2024Review
- Micro-and mesoscale aspects of neurodegeneration in engineered human neural networks carrying the LRRK2 G2019S mutation.Frontiers in cellular neuroscience · 2024Article
- Leucine-rich repeat kinase 2 at a glance.Journal of cell science · 2023Article
- RAB3 phosphorylation by pathogenic LRRK2 impairs trafficking of synaptic vesicle precursors.bioRxiv : the preprint server for biology · 2023Article
- β-Actin: An Emerging Biomarker in Ischemic Stroke.Cellular and molecular neurobiology · 2023Review
- In vivo overexpression of synaptogyrin-3 promotes striatal synaptic dopamine uptake in LRRK2Brain and behavior · 2023Article
- LRRK2 and Proteostasis in Parkinson's Disease.International journal of molecular sciences · 2022Review
- Exploring the focal role of LRRK2 kinase in Parkinson's disease.Environmental science and pollution research international · 2022Review
- LRRK2 regulates actin assembly for spindle migration and mitochondrial function in mouse oocyte meiosis.Journal of molecular cell biology · 2022Article
- Single-cell transcriptomics of human iPSC differentiation dynamics reveal a core molecular network of Parkinson's disease.Communications biology · 2022Article
- LRRK2 decreases microglial actin dynamics by filamentous actin depolymerization and Rac1 inhibition.Animal cells and systems · 2022Article
- Oligomerization of Lrrk controls actin severing and α-synuclein neurotoxicity in vivo.Molecular neurodegeneration · 2021Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 7 institutions in 4 countries.
Funding
Abstract
Mutations in human leucine-rich repeat kinase 2 (Lrrk2), a protein of yet unknown function, are linked to Parkinson's disease caused by degeneration of midbrain dopaminergic neurons. The protein comprises several domains including a GTPase and a kinase domain both affected by several pathogenic mutations. To elucidate the molecular interaction network of endogenous Lrrk2 under stoichiometric constraints, we applied QUICK (quantitative immunoprecipitation combined with knockdown) in NIH3T3 cells. The identified interactome reveals actin isoforms as well as actin-associated proteins involved in actin filament assembly, organization, rearrangement, and maintenance, suggesting that the biological function of Lrrk2 is linked to cytoskeletal dynamics. In fact, we demonstrate Lrrk2 de novo binding to F-actin and its ability to modulate its assembly in vitro. When tested in intact cells, knockdown of Lrrk2 causes morphological alterations in NIH3T3 cells. In developing dopaminergic midbrain primary neurons, Lrrk2 knockdown results in shortened neurite processes, indicating a physiological role of Lrrk2 in cytoskeletal organization and dynamics of dopaminergic neurons. Hence, our results demonstrate that molecular interactions as well as the physiological function of Lrrk2 are closely related to the organization of the actin-based cytoskeleton, a crucial feature of neuronal development and neuron function.
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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.