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
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.