Secretory defect and cytotoxicity: the potential disease mechanisms for the retinitis pigmentosa (RP)-associated interphotoreceptor retinoid-binding protein (IRBP).

ABSTRACT: Interphotoreceptor retinoid-binding protein (IRBP) secreted by photoreceptors plays a pivotal role in photoreceptor survival and function. Recently, a D1080N mutation in IRBP was found in patients with retinitis pigmentosa, a frequent cause of retinal degeneration. The molecular and cellular bases for pathogenicity of the mutation are unknown. Here, we show that the mutation abolishes secretion of IRBP and results in formation of insoluble high molecular weight complexes via disulfide bonds. Co-expression of protein disulfide isomerase A2 that regulates disulfide bond formation or introduction of double Cys-to-Ala substitutions at positions 304 and 1175 in D1080N IRBP promoted secretion of the mutated IRBP. D1080N IRBP was not transported to the Golgi apparatus, but accumulated in the endo

SUBMITTER: Li S 

PROVIDER: S-EPMC3630842 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature