Copa-1 mutants experience heightened endoplasmic reticulum stress sensitivity in a C. elegans COPA Syndrome model.

Abstract

COPA Syndrome is a rare, autosomal dominant autoimmune/autoinflammatory disease caused by mutations in COPA , which codes for the alpha subunit of the Coat Protein Complex I (COPI). COPI coated vesicles move proteins in retrograde from the Golgi Apparatus to the Endoplasmic Reticulum. At the cellular level, COPA mutations cause ER stress, though the downstream genetic mechanisms of COPA Syndrome remain undefined. Here, we model COPA Syndrome in Caenorhabditis elegans , using CRISPR/Cas9 to generate patient alleles in copa-1 , the C. elegans COPA ortholog. The two alleles made thus far are superficially wild type under normal growth conditions. However, these animals demonstrate an increased ER stress sensitivity.