Zhao, Yibo;
Vavouraki, Nikoleta;
Lovering, Ruth C;
Escott-Price, Valentina;
Harvey, Kirsten;
Lewis, Patrick A;
Manzoni, Claudia;
(2023)
Tissue specific LRRK2 interactomes reveal a distinct striatal functional unit.
PLoS Computational Biology
, 19
(1)
, Article e1010847. 10.1371/journal.pcbi.1010847.
(In press).
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Abstract
Mutations in LRRK2 are the most common genetic cause of Parkinson's disease. Despite substantial research efforts, the physiological and pathological role of this multidomain protein remains poorly defined. In this study, we used a systematic approach to construct the general protein-protein interactome around LRRK2, which was then evaluated taking into consideration the differential expression patterns and the co-expression behaviours of the LRRK2 interactors in 15 different healthy tissue types. The LRRK2 interactors exhibited distinct expression features in the brain as compared to the peripheral tissues analysed. Moreover, a high degree of similarity was found for the LRRK2 interactors in putamen, caudate and nucleus accumbens, thus defining a potential LRRK2 functional cluster within the striatum. The general LRRK2 interactome paired with the expression profiles of its members constitutes a powerful tool to generate tissue-specific LRRK2 interactomes. We exemplified the generation of the tissue-specific LRRK2 interactomes and explored the functions highlighted by the "core LRRK2 interactors" in the striatum in comparison with the cerebellum. Finally, we illustrated how the LRRK2 general interactome reported in this manuscript paired with the expression profiles can be used to trace the relationship between LRRK2 and specific interactors of interest, here focusing on the LRRK2 interactors belonging to the Rab protein family.
| Type: | Article |
|---|---|
| Title: | Tissue specific LRRK2 interactomes reveal a distinct striatal functional unit |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pcbi.1010847 |
| Publisher version: | https://doi.org/10.1371/journal.pcbi.1010847 |
| Language: | English |
| Additional information: | © 2023 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10164487 |
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