Axonal Transport Defect in Gigaxonin Deficiency Rescued by Tubastatin A.

ABSTRACT: Giant axonal neuropathy (GAN) is a disease caused by a deficiency of gigaxonin, a mediator of the degradation of intermediate filament (IF) proteins. A lack of gigaxonin alters the turnover of IF proteins, provoking accumulation and disorganization of neurofilaments (NFs) in neurons, a hallmark of the disease. However, the effects of IF disorganization on neuronal function remain unknown. Here, we report that cultured embryonic dorsal root ganglia (DRG) neurons derived from Gan^-/- mice exhibit accumulations of IF proteins and defects in fast axonal transport of organelles. Kymographs generated by time-lapse microscopy revealed substantial reduction of anterograde movements of mitochondria and lysosomes in axons of Gan^-/- DRG neurons. Treatment of Gan^-/- DRG

SUBMITTER: Nath B 

PROVIDER: S-EPMC10457258 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature