@article{a86e7279c623448c8a9e9d64f1e8377b,
title = "Requirement for translocon-associated protein (TRAP) α in insulin biogenesis",
abstract = "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.",
author = "Xin Li and Itani, {Omar A.} and Leena Haataja and Dumas, {Kathleen J.} and Jing Yang and Jeeyeon Cha and Stephane Flibotte and Shih, {Hung Jen} and Delaney, {Colin E.} and Jialu Xu and Ling Qi and Peter Arvan and Ming Liu and Hu, {Patrick J.}",
note = "Funding Information: This work was supported by the American Heart Association Postdoctoral Fellowship Award 14POST20390031 (to O.A.I.) and Innovative Research Grant 11IRG5170009 (to P.J.H.); National Natural Science Foundation of China grants 81830025, 81620108004, and 81570699 (to M.L.); NIH T32DK007061 (to J.C.), R01DK120047 (to L.Q.), R01DK111174 (to L.Q., P.A., and M.L.), R01DK048280 (to P.A.), and R01AG041177 (to P.J.H.); and the American Cancer Society Research Scholar Grant 119640-RSG-10-132-01-DDC (to P.J.H.). Publisher Copyright: Copyright {\textcopyright} 2019 The Authors",
year = "2019",
month = dec,
day = "4",
doi = "10.1126/sciadv.aax0292",
language = "English",
volume = "5",
journal = "Science Advances",
issn = "2375-2548",
number = "12",
}