Computational Analysis of the LRRK2 Interactome

Overview

Journal PeerJ

Specialties Biology
Environmental Health
General Medicine

Date 2015 Mar 5

PMID 25737818

Citations 32

Authors

Claudia Manzoni

Paul Denny

Ruth C Lovering

Patrick A Lewis

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Transcriptomics and weighted protein network analyses of the LRRK2 protein interactome reveal distinct molecular signatures for sporadic and LRRK2 Parkinson's Disease.

Zhao Y, Bracher-Smith M, Li Y, Harvey K, Escott-Price V, Lewis P NPJ Parkinsons Dis. 2024; 10(1):144.

PMID: 39097579 PMC: 11297940. DOI: 10.1038/s41531-024-00761-8.

Dysregulated Wnt and NFAT signaling in a Parkinson's disease LRRK2 G2019S knock-in model.

Wetzel A, Lei S, Liu T, Hughes M, Peng Y, McKay T Sci Rep. 2024; 14(1):12393.

PMID: 38811759 PMC: 11137013. DOI: 10.1038/s41598-024-63130-8.

Leucine-rich repeat kinase 2 at a glance.

Zhu C, Herbst S, Lewis P J Cell Sci. 2023; 136(17).

PMID: 37698513 PMC: 10508695. DOI: 10.1242/jcs.259724.

Tissue specific LRRK2 interactomes reveal a distinct striatal functional unit.

Zhao Y, Vavouraki N, Lovering R, Escott-Price V, Harvey K, Lewis P PLoS Comput Biol. 2023; 19(1):e1010847.

PMID: 36716346 PMC: 9910798. DOI: 10.1371/journal.pcbi.1010847.

Midbrain organoids mimic early embryonic neurodevelopment and recapitulate LRRK2-p.Gly2019Ser-associated gene expression.

Zagare A, Barmpa K, Smajic S, Smits L, Grzyb K, Grunewald A Am J Hum Genet. 2022; 109(2):311-327.

PMID: 35077669 PMC: 8874228. DOI: 10.1016/j.ajhg.2021.12.009.

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