Defective ER associated degradation of a model luminal substrate in yeast carrying a mutation in the 4th ER luminal loop of Sec61p.

ABSTRACT: The major constituent of the eukaryotic ER protein-translocation channel (Sec61p in yeast, Sec61α in higher eukaryotes) shows a high degree of evolutionary conservation from yeast to humans. The vast majority of eukaryotic species have a conserved di-tyrosine in the 4th ER luminal loop. Previously, we discovered through a screen of ethylnitrosourea- (ENU-) mutagenized mice that substitution of the latter of these tyrosines with histidine (Y344H) of the murine Sec61α protein results in diabetes and hepatic steatosis in mice that is a result of ER stress. To further characterize the mechanism behind ER stress in these mice we made the homologous mutation in yeast Sec61p (Y345H). We found that this mutation increased sensitivity of yeast to ER stressing agents and to reduction of Inositol Req

SUBMITTER: Wheeler MC 

PROVIDER: S-EPMC3490007 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature