Diverse CMT2 neuropathies are linked to aberrant G3BP interactions in stress granules  

作　　者：Qinqin Cui 

机构地区：[1]不详

出　　处：《四川生理科学杂志》2023年第2期358-358,共1页Sichuan Journal of Physiological Sciences

摘　　要：Complex diseases often involve the interplay between genetic and environmental factors. Charcot-Marie-Tooth type 2neuropathies (CMT2) are a group of genetically heterogeneous disorders, in which similar peripheral neuropathology isinexplicably caused by various mutated genes. Their possible molecular links remain elusive. Here, we found that uponenvironmental stress, many CMT2-causing mutant proteins adopt similar properties by entering stress granules (SGs), where theyaberrantly interact with G3BP and integrate into SG pathways. For example, glycyl-tRNA synthetase (GlyRS) is translocated fromthe cytoplasm into SGs upon stress, where the mutant GlyRS perturbs the G3BP-centric SG network by aberrantly binding toG3BP. This disrupts SG-mediated stress responses, leading to increased stress vulnerability in motoneurons. Disrupting thisaberrant interaction rescues SG abnormalities and alleviates motor deficits in CMT2D mice. These findings reveal a stressdependentmolecular link across diverse CMT2 mutants and provide a conceptual framework for understanding geneticheterogeneity in light of environmental stress.

关 键 词：stress GRANULES Marie 

分 类 号：Q94[生物学—植物学]