ArticleProceedings of the National Academy of Sciences of the United States of America2023
Localization of PPM1H phosphatase tunes Parkinson's disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- LRRK2: Molecular Mechanisms in Parkinson's Disease.International journal of molecular sciences · 2026Review
- Parkinson's-Linked LRRK2 and GBA1 Mutations Modulate the Peripheral Immune Response to Pseudomonas aeruginosa.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- LRRK2 kinase-mediated accumulation of lysosome-associated phospho-Rabs in tauopathies and synucleinopathies.Acta neuropathologica · 2025Article
- PPM1M, an LRRK2-counteracting, phosphoRab12-preferring phosphatase with a potential link to Parkinson's disease.Cell reports · 2025Article
- Salmonella exploits LRRK2-dependent plasma membrane dynamics to invade host cells.Nature communications · 2025Article
- Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- RAB12-LRRK2 complex suppresses primary ciliogenesis and regulates centrosome homeostasis in astrocytes.Nature communications · 2024Article
- The primary cilium of cholinergic neurons may be a linchpin in the progression of Parkinson's Disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- RAB12-LRRK2 Complex Suppresses Primary Ciliogenesis and Regulates Centrosome Homeostasis in Astrocytes.bioRxiv : the preprint server for biology · 2024Article
- RAB3 phosphorylation by pathogenic LRRK2 impairs trafficking of synaptic vesicle precursors.The Journal of cell biology · 2024Article
- CURTAIN-A unique web-based tool for exploration and sharing of MS-based proteomics data.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Primary cilia in Parkinson's disease: summative roles in signaling pathways, genes, defective mitochondrial function, and substantia nigra dopaminergic neurons.Frontiers in aging neuroscience · 2024Review
- 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
- RAB3 phosphorylation by pathogenic LRRK2 impairs trafficking of synaptic vesicle precursors.bioRxiv : the preprint server for biology · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
PPM1H phosphatase reverses Parkinson's disease-associated, Leucine Rich Repeat Kinase 2-mediated Rab GTPase phosphorylation. We show here that PPM1H relies on an N-terminal amphipathic helix for Golgi localization. The amphipathic helix enables PPM1H to bind to liposomes in vitro, and small, highly curved liposomes stimulate PPM1H activity. We artificially anchored PPM1H to the Golgi, mitochondria, or mother centriole. Our data show that regulation of Rab10 GTPase phosphorylation requires PPM1H access to Rab10 at or near the mother centriole. Moreover, poor colocalization of Rab12 explains in part why it is a poor substrate for PPM1H in cells but not in vitro. These data support a model in which localization drives PPM1H substrate selection and centriolar PPM1H is critical for regulation of Rab GTPase-regulated ciliogenesis. Moreover, Golgi localized PPM1H may maintain active Rab GTPases on the Golgi to carry out their nonciliogenesis-related functions in membrane trafficking.
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