ArticleFrontiers in molecular neuroscience2018
RAB7L1-Mediated Relocalization of LRRK2 to the Golgi Complex Causes Centrosomal Deficits via RAB8A.
Article in Frontiers in molecular neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Rab8a dysregulation in Parkinson's disease: A convergence of genetic and molecular pathologies.Molecular biology reports · 2026Review
- Organelle-Targeted Nanotherapeutics for Parkinson's Disease: From Pathogenesis to Preclinical Strategies and Translational Challenges.International journal of nanomedicine · 2026Review
- Review
- Phosphorylation of Rab29 at Ser185 regulates its localization and role in the lysosomal stress response in concert with LRRK2.Journal of cell science · 2023Article
- Insights into the cellular consequences of LRRK2-mediated Rab protein phosphorylation.Biochemical Society transactions · 2023Review
- The small GTPase Rit2 modulates LRRK2 kinase activity, is required for lysosomal function and protects against alpha-synuclein neuropathology.NPJ Parkinson's disease · 2023Article
- The function of Golgi apparatus in LRRK2-associated Parkinson's disease.Frontiers in molecular neuroscience · 2023Review
- Article
- The Role of Rab Proteins in Parkinson's Disease Synaptopathy.Biomedicines · 2022Review
- Rab GTPases in Parkinson's disease: a primer.Essays in biochemistry · 2021Article
- LRRK2 along the Golgi and lysosome connection: a jamming situation.Biochemical Society transactions · 2021Review
- Modelling the functional genomics of Parkinson's disease in Caenorhabditis elegans: LRRK2 and beyond.Bioscience reports · 2021Review
- Increased LRRK2 kinase activity alters neuronal autophagy by disrupting the axonal transport of autophagosomes.Current biology : CB · 2021Article
- Combined Knockout of Lrrk2 and Rab29 Does Not Result in Behavioral Abnormalities in vivo.Journal of Parkinson's disease · 2021Article
- Endogenous Rab29 does not impact basal or stimulated LRRK2 pathway activity.The Biochemical journal · 2020Article
- Endocytic membrane trafficking in the control of centrosome function.Current opinion in cell biology · 2020Review
- Distinct Roles for RAB10 and RAB29 in Pathogenic LRRK2-Mediated Endolysosomal Trafficking Alterations.Cells · 2020Article
- The Emerging Functions of LRRK2 and Rab GTPases in the Endolysosomal System.Frontiers in neuroscience · 2020Review
- LRRK2 and the Endolysosomal System in Parkinson's Disease.Journal of Parkinson's disease · 2020Review
- LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same.Molecular neurodegeneration · 2019Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the LRRK2 gene cause autosomal-dominant Parkinson's disease (PD), and both LRRK2 as well as RAB7L1 have been implicated in increased susceptibility to idiopathic PD. RAB7L1 has been shown to increase membrane-association and kinase activity of LRRK2, and both seem to be mechanistically implicated in the same pathway. Another RAB protein, RAB8A, has been identified as a prominent LRRK2 kinase substrate, and our recent work demonstrates that aberrant LRRK2-mediated phosphorylation of RAB8A leads to centrosomal alterations. Here, we show that RAB7L1 recruits LRRK2 to the Golgi complex, which causes accumulation of phosphorylated RAB8A in a pericentrosomal/centrosomal location as well as centrosomal deficits identical to those observed with pathogenic LRRK2. The centrosomal alterations induced by wildtype LRRK2 in the presence of RAB7L1 depend on Golgi integrity. This is in contrast to pathogenic LRRK2 mutants, which cause centrosomal deficits independent of Golgi integrity or largely independent on RAB7L1 expression. Furthermore, centrosomal alterations in the presence of wildtype LRRK2 and RAB7L1 are at least in part mediated by aberrant LRRK2-mediated RAB8A phosphorylation, as abolished by kinase inhibitors and reduced upon knockdown of RAB8A. These results indicate that pathogenic LRRK2, as well as increased levels of RAB7L1, cause centrosomal deficits in a manner dependent on aberrant RAB8A phosphorylation and centrosomal/pericentrosomal accumulation, suggesting that centrosomal cohesion deficits may comprise a useful cellular readout for a broader spectrum of the disease.
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