Anoop Arunagiri, Maroof Alam, Leena Haataja, Hassan Draz, Bashiyer Alasad, Praveen Samy, Nadeed Sadique, Yue Tong, Ying Cai, Hadis Shakeri, Federica Fantuzzi, Hazem Ibrahim, Insook Jang, Vaibhav Sidarala, Scott A Soleimanpour, Leslie S Satin, Timo Otonkoski, Miriam Cnop, Pamela Itkin-Ansari, Randal J Kaufman, Ming Liu, Peter Arvan
Primary defects in folding of mutant proinsulin can cause dominant-negative proinsulin accumulation in the endoplasmic reticulum (ER), impaired anterograde proinsulin trafficking, perturbed ER homeostasis, diminished insulin production, and β-cell dysfunction. Conversely, if primary impairment of ER-to-Golgi trafficking (which also perturbs ER homeostasis) drives misfolding of nonmutant proinsulin-this might suggest bi-directional entry into a common pathological phenotype (proinsulin misfolding, perturbed ER homeostasis, and deficient ER export of proinsulin) that can culminate in diminished insulin storage and diabetes...
April 2024: Protein Science