ArticleJournal of neurochemistry2015
Leucine-rich repeat kinase 2 interacts with p21-activated kinase 6 to control neurite complexity in mammalian brain.
Article in Journal of neurochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 70 citations in OpenAlex.
- A complex of MAST1 and 14-3-3η regulates Tau phosphorylation in the developing cortex.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Regulation between LRRK2 and PP2A signaling in cellular models of Parkinson's disease.The Biochemical journal · 2026Article
- Cadmium-induced gut dysbiosis precedes the onset of hippocampus-dependent learning and memory deficits in mice.Toxicology · 2025Article
- Phosphorylation at the Helm: Kinase-Mediated Regulation of Primary Cilia Assembly and Disassembly.Cytoskeleton (Hoboken, N.J.) · 2025Review
- LRRK2 and the fragile synapse: a molecular prelude to Parkinson's disease?The Biochemical journal · 2025Review
- PAK6 rescues pathogenic LRRK2-mediated ciliogenesis and centrosomal cohesion defects in a mutation-specific manner.Cell death & disease · 2024Article
- Prospective Role of PAK6 and 14-3-3γ as Biomarkers for Parkinson's Disease.Journal of Parkinson's disease · 2024Article
- Insights into the cellular consequences of LRRK2-mediated Rab protein phosphorylation.Biochemical Society transactions · 2023Review
- PAK6-mediated phosphorylation of PPP2R2C regulates LRRK2-PP2A complex formation.Frontiers in molecular neuroscience · 2023Article
- Dementia with Lewy bodies post-mortem brains reveal differentially methylated CpG sites with biomarker potential.Communications biology · 2022Article
- Rho family GTPase signaling through type II p21-activated kinases.Cellular and molecular life sciences : CMLS · 2022Review
- The p21-activated kinases in neural cytoskeletal remodeling and related neurological disorders.Protein & cell · 2022Review
- Role of DNMTs in the Brain.Advances in experimental medicine and biology · 2022Review
- Review
- Article
- Parkinson's Disease-Associated LRRK2 Interferes with Astrocyte-Mediated Alpha-Synuclein Clearance.Molecular neurobiology · 2021Article
- PAK4 suppresses motor neuron degeneration in hSOD1Cell proliferation · 2021Article
- Article
- The Role of p21-Activated Kinases in Cancer and Beyond: Where Are We Heading?Frontiers in cell and developmental biology · 2021Review
- Pathogenic LRRK2 requires secondary factors to induce cellular toxicity.Bioscience reports · 2020Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
Leucine-rich repeat kinase 2 (LRRK2) is a causative gene for Parkinson's disease, but the physiological function and the mechanism(s) by which the cellular activity of LRRK2 is regulated are poorly understood. Here, we identified p21-activated kinase 6 (PAK6) as a novel interactor of the GTPase/ROC domain of LRRK2. p21-activated kinases are serine-threonine kinases that serve as targets for the small GTP binding proteins Cdc42 and Rac1 and have been implicated in different morphogenetic processes through remodeling of the actin cytoskeleton such as synapse formation and neuritogenesis. Using an in vivo neuromorphology assay, we show that PAK6 is a positive regulator of neurite outgrowth and that LRRK2 is required for this function. Analyses of post-mortem brain tissue from idiopathic and LRRK2 G2019S carriers reveal an increase in PAK6 activation state, whereas knock-out LRRK2 mice display reduced PAK6 activation and phosphorylation of PAK6 substrates. Taken together, these results support a critical role of LRRK2 GTPase domain in cytoskeletal dynamics in vivo through the novel interactor PAK6, and provide a valuable platform to unravel the mechanism underlying LRRK2-mediated pathophysiology. We propose p21-activated kinase 6 (PAK6) as a novel interactor of leucine-rich repeat kinase 2 (LRRK2), a kinase involved in Parkinson's disease (PD). In health, PAK6 regulates neurite complexity in the brain and LRRK2 is required for its function, (a) whereas PAK6 is aberrantly activated in LRRK2-linked PD brain (b) suggesting that LRRK2 toxicity is mediated by PAK6.
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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.