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Requirement for translocon-associated protein (TRAP) ? 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 ? (TRAP?), 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 ? cells reveal that TRAP? 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 TRAP? gene with susceptibility to type 2 diabetes and pancreatic ? cell dysfunction suggests that impairment of preproinsulin translocation and proinsulin trafficking may contribute to the pathogenesis of type 2 diabetes.

SUBMITTER: Li X

PROVIDER: S-EPMC6892615 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Requirement for translocon-associated protein (TRAP) α in insulin biogenesis.

Li Xin X Itani Omar A OA Haataja Leena L Dumas Kathleen J KJ Yang Jing J Cha Jeeyeon J Flibotte Stephane S Shih Hung-Jen HJ Delaney Colin E CE Xu Jialu J Qi Ling L Arvan Peter P Liu Ming M Hu Patrick J PJ

Science advances 20191204 12

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 <i>Caenorhabditis elegans</i> and biochemical studies in pancreatic β cells reveal that TRAPα deletion impairs preproinsulin translocation while unexpectedly disrup ...[more]

PMID: 31840061

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