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Tissue specific LRRK2 interactomes reveal a distinct functional unit within the striatum

Yibo Zhao, Nikoleta Vavouraki, Ruth C Lovering, View ORCID ProfileValentina Escott-Price, Kirsten Harvey, Patrick A Lewis, View ORCID ProfileClaudia Manzoni
doi: https://doi.org/10.1101/2022.06.28.497918
Yibo Zhao
1University College London, School of Pharmacy, London, UK
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Nikoleta Vavouraki
2University of Reading, School of Pharmacy, Reading, UK
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Ruth C Lovering
3University College London, Institute for Cardiovascular Disease, London, UK
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Valentina Escott-Price
4University of Cardiff, Division of Neuroscience and Mental Health, Cardiff, UK
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  • ORCID record for Valentina Escott-Price
Kirsten Harvey
1University College London, School of Pharmacy, London, UK
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Patrick A Lewis
5Royal Veterinary College, London, UK
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Claudia Manzoni
1University College London, School of Pharmacy, London, UK
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  • ORCID record for Claudia Manzoni
  • For correspondence: c.manzoni@ucl.ac.uk
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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 differentiated into 15 tissue-specific interactomes taking into consideration the differential expression patterns and the co-expression behaviours of the LRRK2 interactors in different healthy tissues. 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. We also explored the functions highlighted by the “core LRRK2 interactors” within each tissue and illustrated how the LRRK2 interactomes can be used as a tool to trace the relationship between LRRK2 and specific interactors of interest, here exemplified with a study focused on the LRRK2 interactors belonging to the Rab protein family.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted June 28, 2022.
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Tissue specific LRRK2 interactomes reveal a distinct functional unit within the striatum
Yibo Zhao, Nikoleta Vavouraki, Ruth C Lovering, Valentina Escott-Price, Kirsten Harvey, Patrick A Lewis, Claudia Manzoni
bioRxiv 2022.06.28.497918; doi: https://doi.org/10.1101/2022.06.28.497918
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Tissue specific LRRK2 interactomes reveal a distinct functional unit within the striatum
Yibo Zhao, Nikoleta Vavouraki, Ruth C Lovering, Valentina Escott-Price, Kirsten Harvey, Patrick A Lewis, Claudia Manzoni
bioRxiv 2022.06.28.497918; doi: https://doi.org/10.1101/2022.06.28.497918

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