Endocrinopathies in the Family of Endoplasmic Reticulum (ER) Storage Diseases: Disorders of Protein Trafficking and the Role of ER Molecular Chaperones

I. Introduction A. Overview B. Protein folding in the ER C. Supervised folding: the concept of molecular chaperones and folding catalysts D. Co- and posttranslational modifications are factors that can influence folding II. ER Molecular Chaperones, Folding Catalysts, and Molecular Escorts A. Binding protein (BiP) B. GRP94 C. Calnexin and calreticulin D. Disulfide isomerase and prolyl isomerase: families of folding catalysts E. ERp72 and ER60 F. HSP47 G. Molecular escorts: pro-peptides, transport subunits, receptor-associated protein (RAP), and 7B2 III. Models of ER to Golgi Traffic Influence Models of Quality Control A. Escape from ER retention as one hypothesis to explain anterograde protein traffic from the ER B. Cargo receptors as another hypothesis to explain anterograde protein traffic from the ER C. What provides quality control of ER export? D. ER-associated degradation IV. Endocrinopathies as Models of Defective Protein Export A. Congenital hypothyroid goiter with thyroglobulin deficiency B. Familial neurohypophyseal diabetes insipidus C. Osteogenesis imperfecta and disorders of procollagen biosynthesis D. ERSDs affecting lipoprotein metabolism E. Other selected nonendocrine and endocrine ERSDs V. Summary: A Proposed Classification of ERSDs