Myopathic lamin mutations cause reductive stress and activate the nrf2/keap-1 pathway.

ABSTRACT: Mutations in the human LMNA gene cause muscular dystrophy by mechanisms that are incompletely understood. The LMNA gene encodes A-type lamins, intermediate filaments that form a network underlying the inner nuclear membrane, providing structural support for the nucleus and organizing the genome. To better understand the pathogenesis caused by mutant lamins, we performed a structural and functional analysis on LMNA missense mutations identified in muscular dystrophy patients. These mutations perturb the tertiary structure of the conserved A-type lamin Ig-fold domain. To identify the effects of these structural perturbations on lamin function, we modeled these mutations in Drosophila Lamin C and expressed the mutant lamins in muscle. We found that the structural perturbations had minimal dom

SUBMITTER: Dialynas G 

PROVIDER: S-EPMC4440730 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature