Biljana Ermanoska, Bob Asselbergh, Laura Morant, Maria-Luise Petrovic-Erfurth, Seyyedmohsen Hosseinibarkooie, Ricardo Leitão-Gonçalves, Leonardo Almeida-Souza, Sven Bervoets, Litao Sun, LaTasha Lee, Derek Atkinson, Akram Khanghahi, Ivaylo Tournev, Patrick Callaerts, Patrik Verstreken, Xiang-Lei Yang, Brunhilde Wirth, Avital A Rodal, Vincent Timmerman, Bruce L Goode, Tanja A Godenschwege, Albena Jordanova
Dominant mutations in tyrosyl-tRNA synthetase (YARS1) and six other tRNA ligases cause Charcot-Marie-Tooth peripheral neuropathy (CMT). Loss of aminoacylation is not required for their pathogenicity, suggesting a gain-of-function disease mechanism. By an unbiased genetic screen in Drosophila, we link YARS1 dysfunction to actin cytoskeleton organization. Biochemical studies uncover yet unknown actin-bundling property of YARS1 to be enhanced by a CMT mutation, leading to actin disorganization in the Drosophila nervous system, human SH-SY5Y neuroblastoma cells, and patient-derived fibroblasts...
March 8, 2023: Nature Communications