Lisa E L Romano, Wen Yih Aw, Kathryn M Hixson, Tatiana V Novoselova, Tammy M Havener, Stefanie Howell, Bonnie Taylor-Blake, Charlotte L Hall, Lei Xing, Josh Beri, Suran Nethisinghe, Laura Perna, Abubakar Hatimy, Ginevra Chioccioli Altadonna, Lee M Graves, Laura E Herring, Anthony J Hickey, Konstantinos Thalassinos, J Paul Chapple, Justin M Wolter
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset cerebellar ataxia caused by mutations in SACS, which encodes the protein sacsin. Cellular ARSACS phenotypes include mitochondrial dysfunction, intermediate filament disorganization, and progressive death of cerebellar Purkinje neurons. It is unclear why the loss of sacsin causes these deficits or why they manifest as cerebellar ataxia. Here, we perform multi-omic profiling in sacsin knockout (KO) cells and identify alterations in microtubule dynamics and mislocalization of focal adhesion (FA) proteins, including multiple integrins...
November 1, 2022: Cell Reports