PT  - JOURNAL ARTICLE
AU  - Li, Xin
AU  - Itani, Omar A.
AU  - Haataja, Leena
AU  - Dumas, Kathleen J.
AU  - Yang, Jing
AU  - Cha, Jeeyeon
AU  - Flibotte, Stephane
AU  - Shih, Hung-Jen
AU  - Delaney, Colin E.
AU  - Xu, Jialu
AU  - Qi, Ling
AU  - Arvan, Peter
AU  - Liu, Ming
AU  - Hu, Patrick J.
TI  - Requirement for translocon-associated protein (TRAP) α in insulin biogenesis
AID  - 10.1126/sciadv.aax0292
DP  - 2019 Dec 01
TA  - Science Advances
PG  - eaax0292
VI  - 5
IP  - 12
4099  - http://advances.sciencemag.org/content/5/12/eaax0292.short
4100  - http://advances.sciencemag.org/content/5/12/eaax0292.full
SO  - Sci Adv2019 Dec 01; 5
AB  - The mechanistic basis for the biogenesis of peptide hormones and growth factors is poorly understood. Here, we show that the conserved endoplasmic reticulum membrane translocon-associated protein α (TRAPα), also known as signal sequence receptor 1, plays a critical role in the biosynthesis of insulin. Genetic analysis in the nematode Caenorhabditis elegans and biochemical studies in pancreatic β cells reveal that TRAPα deletion impairs preproinsulin translocation while unexpectedly disrupting distal steps in insulin biogenesis including proinsulin processing and secretion. The association of common intronic single-nucleotide variants in the human TRAPα gene with susceptibility to type 2 diabetes and pancreatic β cell dysfunction suggests that impairment of preproinsulin translocation and proinsulin trafficking may contribute to the pathogenesis of type 2 diabetes.