An integrated transcriptomics and proteomics analysis reveals functional endocytic dysregulation caused by mutations in LRRK2

Natalie Connor-Robson; Heather Booth; Jeffrey G. Martin; Benbo Gao; Kejie Li; Natalie Doig; Jane Vowles; Cathy Browne; Laura Klinger; Peter Juhasz; Christine Klein; Sally A. Cowley; Paul Bolam; Warren Hirst; Richard Wade-Martins

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An integrated transcriptomics and proteomics analysis reveals functional endocytic dysregulation caused by mutations in LRRK2

Highlights iPSC-derived dopaminergic neurons from LRRK2 patients show extensive endocytic changes. Integrated proteomic and transcriptomic approach reveals dysregulation of 25 RABs. Functional impairment of clathrin mediated endocytosis in LRRK2 iPSC-dopaminergic neurons. Aged LRRK2 rats also show similar perturbations of key endocytic proteins. LRRK2 human post-mortem tissue shows upregulation of clathrin and endophilin.

More information Original publication

DOI

10.1016/j.nbd.2019.04.005

Type

Journal article

Publication Date

7/2019

Volume

127

Pages

512 - 526

Addresses

https://www.sciencedirect.com/science/article/pii/S0969996119300968

Keywords

LRRK2 iPSC-dopaminergic neurons, post-mortem, Integrated proteomic and transcriptomic approach