Proteomic analysis reveals co-ordinated alterations in protein synthesis and degradation pathways in LRRK2 knockout mice

ABSTRACT: Mutations in leucine-rich repeat kinase 2 (LRRK2) segregate with familial Parkinson’s disease (PD) and genetic variation in LRRK2 contributes to risk of sporadic disease. Although knockout of LRRK2 or knock-in of pathogenic mutations into the mouse germline does not result in a PD phenotype, several defects have been reported in the kidneys of LRRK2 knockout mice. To understand LRRK2 function in vivo, we used an unbiased approach to determine which protein pathways are affected in LRRK2 knockout kidneys. We performed two iTRAQ screens on cytosol- and microsome-enriched fractions from 12-month old LRRK2-KO and G2019S knockin kidneys compared to wild type controls. We nominated changes in cytoskeletal-associated proteins, lysosomal proteases, proteins involved in vesicular trafficking and in control of protein translation in LRRK2-KO. Changes were not seen in mice expressing the pathogenic G2019S LRRK2 mutant.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Kidney

SUBMITTER: Jinhui Ding  

LAB HEAD: Mark R Cookson

PROVIDER: PXD008531 | Pride | 2022-03-01

REPOSITORIES: Pride