Cellular stress due to impairment of collagen prolyl hydroxylation complex is rescued by the chaperone 4-phenylbutyrate.

ABSTRACT: Osteogenesis imperfecta (OI) types VII, VIII and IX, caused by recessive mutations in cartilage-associated protein (CRTAP), prolyl-3-hydroxylase 1 (P3H1) and cyclophilin B (PPIB), respectively, are characterized by the synthesis of overmodified collagen. The genes encode for the components of the endoplasmic reticulum (ER) complex responsible for the 3-hydroxylation of specific proline residues in type I collagen. Our study dissects the effects of mutations in the proteins of the complex on cellular homeostasis, using primary fibroblasts from seven recessive OI patients. In all cell lines, the intracellular retention of overmodified type I collagen molecules causes ER enlargement associated with the presence of protein aggregates, activation of the PERK branch of the u

SUBMITTER: Besio R 

PROVIDER: S-EPMC6602311 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature