ArticleHuman molecular genetics2017
GTP binding regulates cellular localization of Parkinson's disease-associated LRRK2.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Article
- Parkinson's disease-associated LRRK2 risk variant, G2385R, enhances Rab substrate phosphorylation and impairs neuronal integrity.Human molecular genetics · 2026Article
- The structural basis for LRRK2's activation and autoinhibition.bioRxiv : the preprint server for biology · 2026Article
- Regulation between LRRK2 and PP2A signaling in cellular models of Parkinson's disease.The Biochemical journal · 2026Article
- Phospho-mimic βIII-tubulin rescues microtubule and cardiac defects in Duchenne muscular dystrophy mice.Journal of molecular and cellular cardiology · 2026Article
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Article
- Structural biology of Parkinson's disease-associated leucine-rich repeat kinase 2 (LRRK2).The Journal of biological chemistry · 2025Review
- Cryo-electron tomography reveals the microtubule-bound form of inactive LRRK2.bioRxiv : the preprint server for biology · 2025Article
- A designed ankyrin-repeat protein that targets Parkinson's disease-associated LRRK2.The Journal of biological chemistry · 2024Article
- G2019S selective LRRK2 kinase inhibitor abrogates mitochondrial DNA damage.NPJ Parkinson's disease · 2024Article
- Inhibition of Parkinson's disease-related LRRK2 by type I and type II kinase inhibitors: Activity and structures.Science advances · 2023Article
- Insights into the cellular consequences of LRRK2-mediated Rab protein phosphorylation.Biochemical Society transactions · 2023Review
- Capturing Differences in the Regulation of LRRK2 Dynamics and Conformational States by Small Molecule Kinase Inhibitors.ACS chemical biology · 2023Article
- Impact of 100 LRRK2 variants linked to Parkinson's disease on kinase activity and microtubule binding.The Biochemical journal · 2022Article
- The LRRK2 signaling network converges on a centriolar phospho-Rab10/RILPL1 complex to cause deficits in centrosome cohesion and cell polarization.Biology open · 2022Article
- Functional Analyses of Two Novel LRRK2 Pathogenic Variants in Familial Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2022Article
- Pathogenic LRRK2 regulates centrosome cohesion via Rab10/RILPL1-mediated CDK5RAP2 displacement.iScience · 2022Article
- Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in leucine-rich repeat kinase 2 (LRRK2) comprise the most common cause of familial Parkinson's disease (PD), and sequence variants modify risk for sporadic PD. Previous studies indicate that LRRK2 interacts with microtubules (MTs) and alters MT-mediated vesicular transport processes. However, the molecular determinants within LRRK2 required for such interactions have remained unknown. Here, we report that most pathogenic LRRK2 mutants cause relocalization of LRRK2 to filamentous structures which colocalize with a subset of MTs, and an identical relocalization is seen upon pharmacological LRRK2 kinase inhibition. The pronounced colocalization with MTs does not correlate with alterations in LRRK2 kinase activity, but rather with increased GTP binding. Synthetic mutations which impair GTP binding, as well as LRRK2 GTP-binding inhibitors profoundly interfere with the abnormal localization of both pathogenic mutant as well as kinase-inhibited LRRK2. Conversely, addition of a non-hydrolyzable GTP analog to permeabilized cells enhances the association of pathogenic or kinase-inhibited LRRK2 with MTs. Our data elucidate the mechanism underlying the increased MT association of select pathogenic LRRK2 mutants or of pharmacologically kinase-inhibited LRRK2, with implications for downstream MT-mediated transport events.
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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.