Computational analysis of the LRRK2 interactome
LRRK2 was identified in 2004 as the causative protein product of the Parkinson’s disease locus designated PARK8. In the decade since then, genetic studies have revealed at least 6 dominant mutations in LRRK2 linked to Parkinson’s disease, alongside one associated with cancer. It is now well establis...
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| Format: | Article |
| Language: | English |
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PeerJ Inc.
2015-02-01
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| Series: | PeerJ |
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| Online Access: | https://peerj.com/articles/778.pdf |
| _version_ | 1797421834092675072 |
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| author | Claudia Manzoni Paul Denny Ruth C. Lovering Patrick A. Lewis |
| author_facet | Claudia Manzoni Paul Denny Ruth C. Lovering Patrick A. Lewis |
| author_sort | Claudia Manzoni |
| collection | DOAJ |
| description | LRRK2 was identified in 2004 as the causative protein product of the Parkinson’s disease locus designated PARK8. In the decade since then, genetic studies have revealed at least 6 dominant mutations in LRRK2 linked to Parkinson’s disease, alongside one associated with cancer. It is now well established that coding changes in LRRK2 are one of the most common causes of Parkinson’s. Genome-wide association studies (GWAs) have, more recently, reported single nucleotide polymorphisms (SNPs) around the LRRK2 locus to be associated with risk of developing sporadic Parkinson’s disease and inflammatory bowel disorder. The functional research that has followed these genetic breakthroughs has generated an extensive literature regarding LRRK2 pathophysiology; however, there is still no consensus as to the biological function of LRRK2. To provide insight into the aspects of cell biology that are consistently related to LRRK2 activity, we analysed the plethora of candidate LRRK2 interactors available through the BioGRID and IntAct data repositories. We then performed GO terms enrichment for the LRRK2 interactome. We found that, in two different enrichment portals, the LRRK2 interactome was associated with terms referring to transport, cellular organization, vesicles and the cytoskeleton. We also verified that 21 of the LRRK2 interactors are genetically linked to risk for Parkinson’s disease or inflammatory bowel disorder. The implications of these findings are discussed, with particular regard to potential novel areas of investigation. |
| first_indexed | 2024-03-09T07:23:08Z |
| format | Article |
| id | doaj.art-a7dcd8d616b2493ab9bc1a26837f153b |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T07:23:08Z |
| publishDate | 2015-02-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-a7dcd8d616b2493ab9bc1a26837f153b2023-12-03T07:14:25ZengPeerJ Inc.PeerJ2167-83592015-02-013e77810.7717/peerj.778778Computational analysis of the LRRK2 interactomeClaudia Manzoni0Paul Denny1Ruth C. Lovering2Patrick A. Lewis3School of Pharmacy, University of Reading, Whiteknights, Reading, UKInstitute of Cardiovascular Science, University College London, London, UKInstitute of Cardiovascular Science, University College London, London, UKSchool of Pharmacy, University of Reading, Whiteknights, Reading, UKLRRK2 was identified in 2004 as the causative protein product of the Parkinson’s disease locus designated PARK8. In the decade since then, genetic studies have revealed at least 6 dominant mutations in LRRK2 linked to Parkinson’s disease, alongside one associated with cancer. It is now well established that coding changes in LRRK2 are one of the most common causes of Parkinson’s. Genome-wide association studies (GWAs) have, more recently, reported single nucleotide polymorphisms (SNPs) around the LRRK2 locus to be associated with risk of developing sporadic Parkinson’s disease and inflammatory bowel disorder. The functional research that has followed these genetic breakthroughs has generated an extensive literature regarding LRRK2 pathophysiology; however, there is still no consensus as to the biological function of LRRK2. To provide insight into the aspects of cell biology that are consistently related to LRRK2 activity, we analysed the plethora of candidate LRRK2 interactors available through the BioGRID and IntAct data repositories. We then performed GO terms enrichment for the LRRK2 interactome. We found that, in two different enrichment portals, the LRRK2 interactome was associated with terms referring to transport, cellular organization, vesicles and the cytoskeleton. We also verified that 21 of the LRRK2 interactors are genetically linked to risk for Parkinson’s disease or inflammatory bowel disorder. The implications of these findings are discussed, with particular regard to potential novel areas of investigation.https://peerj.com/articles/778.pdfLRRK2InteractomeProtein–protein interactionsParkinson’s diseaseGO terms enrichment |
| spellingShingle | Claudia Manzoni Paul Denny Ruth C. Lovering Patrick A. Lewis Computational analysis of the LRRK2 interactome PeerJ LRRK2 Interactome Protein–protein interactions Parkinson’s disease GO terms enrichment |
| title | Computational analysis of the LRRK2 interactome |
| title_full | Computational analysis of the LRRK2 interactome |
| title_fullStr | Computational analysis of the LRRK2 interactome |
| title_full_unstemmed | Computational analysis of the LRRK2 interactome |
| title_short | Computational analysis of the LRRK2 interactome |
| title_sort | computational analysis of the lrrk2 interactome |
| topic | LRRK2 Interactome Protein–protein interactions Parkinson’s disease GO terms enrichment |
| url | https://peerj.com/articles/778.pdf |
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