ArticleThe Journal of cell biology2019
Membrane association but not identity is required for LRRK2 activation and phosphorylation of Rab GTPases.
Article in The Journal of cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 106 citations in OpenAlex.
- Preformed fibrils of α-synuclein rapidly activate LRRK2 on early endosomes, driving Rab5 phosphorylation and disrupting endolysosomal and synaptic function.NPJ Parkinson's disease · 2026Article
- Elucidating the molecular interplay between LRRK2 and Rab GTPases.bioRxiv : the preprint server for biology · 2026Article
- Lysosomal swelling triggers LRRK2 activity.bioRxiv : the preprint server for biology · 2025Article
- Role of LRRK2 in axonal transport and Parkinson's disease.The Biochemical journal · 2025Review
- Salmonella exploits LRRK2-dependent plasma membrane dynamics to invade host cells.Nature communications · 2025Article
- A STING-CASM-GABARAP pathway activates LRRK2 at lysosomes.The Journal of cell biology · 2025Article
- Intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase-dependent mechanism.eLife · 2024Article
- Impairment of the trans-Golgi-Lysosomal Pathway Accelerates Dopaminergic Neuronal Senescence in LRRK2Aging and disease · 2024Article
- Mechanisms of lysosomal tubulation and sorting driven by LRRK2.Biochemical Society transactions · 2024Review
- RAB3 phosphorylation by pathogenic LRRK2 impairs trafficking of synaptic vesicle precursors.The Journal of cell biology · 2024Article
- Salmonella exploits membrane reservoirs for invasion of host cells.Nature communications · 2024Article
- Rab29-dependent asymmetrical activation of leucine-rich repeat kinase 2.Science (New York, N.Y.) · 2023Article
- Review
- Localization of PPM1H phosphatase tunes Parkinson's disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Genome-wide screen reveals Rab12 GTPase as a critical activator of Parkinson's disease-linked LRRK2 kinase.eLife · 2023Article
- Article
- Membrane remodeling properties of the Parkinson's disease protein LRRK2.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- RAB3 phosphorylation by pathogenic LRRK2 impairs trafficking of synaptic vesicle precursors.bioRxiv : the preprint server for biology · 2023Article
- Phosphorylation of Rab29 at Ser185 regulates its localization and role in the lysosomal stress response in concert with LRRK2.Journal of cell science · 2023Article
- Different pieces of the same puzzle: a multifaceted perspective on the complex biological basis of Parkinson's disease.NPJ Parkinson's disease · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
LRRK2 kinase mutations cause familial Parkinson's disease and increased phosphorylation of a subset of Rab GTPases. Rab29 recruits LRRK2 to the trans-Golgi and activates it there, yet some of LRRK2's major Rab substrates are not on the Golgi. We sought to characterize the cell biology of LRRK2 activation. Unlike other Rab family members, we show that Rab29 binds nucleotide weakly, is poorly prenylated, and is not bound to GDI in the cytosol; nevertheless, Rab29 only activates LRRK2 when it is membrane bound and GTP bound. Mitochondrially anchored, GTP-bound Rab29 is both a LRRK2 substrate and activator, and it drives accumulation of active LRRK2 and phosphorylated Rab10 on mitochondria. Importantly, mitochondrially anchored LRRK2 is much less capable of phosphorylating plasma membrane-anchored Rab10 than soluble LRRK2. These data support a model in which LRRK2 associates with and dissociates from distinct membrane compartments to phosphorylate Rab substrates; if anchored, LRRK2 can modify misdelivered Rab substrates that then become trapped there because GDI cannot retrieve them.
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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.