Requirement for translocon-associated protein (TRAP) α in insulin biogenesis
| Autor: | Xin Li, Jing Yang, Kathleen J. Dumas, Ling Qi, Peter Arvan, Leena Haataja, Hung-Jen Shih, Patrick J. Hu, Stephane Flibotte, Colin Delaney, Jeeyeon Cha, Jialu Xu, Omar A. Itani, Ming Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Signal peptide
Preproinsulin Receptors Peptide medicine.medical_treatment Recombinant Fusion Proteins Receptors Cytoplasmic and Nuclear 03 medical and health sciences 0302 clinical medicine Insulin Secretion medicine Animals Insulin Secretion Protein Precursors Receptor Caenorhabditis elegans Caenorhabditis elegans Proteins Research Articles 030304 developmental biology Proinsulin 0303 health sciences Multidisciplinary Endoplasmic reticulum membrane Membrane Glycoproteins biology Chemistry Endoplasmic reticulum Calcium-Binding Proteins SciAdv r-articles Life Sciences Cell Biology Endoplasmic Reticulum Stress Cell biology Insulin receptor Secretory protein biology.protein hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Biogenesis Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | A forward genetic screen in C. elegans leads to the discovery of a role for a conserved ER membrane protein in insulin biogenesis. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|