N-acetyl-D-glucosamine kinase binds dynein light chain roadblock 1 and promotes protein aggregate clearance.

ABSTRACT: Emerging evidence indicates that neurodegenerative diseases (NDs) result from a failure to clear toxic protein aggregates rather than from their generation. We previously showed N-acetylglucosamine kinase (NAGK) promotes dynein functionality and suggested this might promote aggregate removal and effectively address proteinopathies. Here, we report NAGK interacts with dynein light chain roadblock type 1 (DYNLRB1) and efficiently suppresses mutant huntingtin (mHtt) (Q74) and α-synuclein (α-syn) A53T aggregation in mouse brain cells. A kinase-inactive NAGK_D107A also efficiently cleared Q74 aggregates. Yeast two-hybrid selection and in silico protein-protein docking analysis showed the small domain of NAGK (NAGK-D_S) binds to the C-terminal of DYNLRB1. Furthermore, a small

SUBMITTER: Ripon MKH 

PROVIDER: S-EPMC7427805 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature