PRAP1 is a novel lipid-binding protein that promotes lipid absorption by facilitating MTTP-mediated lipid transport
| Autor: | Ching-Shu Suen, Chih-Syuan Liu, Ming-Jing Hwang, Hubert W Peng, Hsin-Chou Yang, Chia-Jen Lee, Tzu-Yuan Chiu, Yu-Jen Liang, Hsin-Fang Yang-Yen, Hung-Ta Chen, Jeffrey J.Y. Yen, M. Mahmood Hussain |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
HFD high-fat diet Very low-density lipoprotein PDI protein disulfide isomerase Pregnancy Proteins PRAP1 PRAP1 proline-rich acidic protein 1 Biochemistry Microsomal triglyceride transfer protein Mice VLDL very low-density lipoprotein Protein disulfide-isomerase Ternary complex Mice Knockout lipid transport apoB apolipoprotein B TG triglyceride biology Chemistry MTTP microsomal triglyceride transfer protein Cell biology Apolipoprotein B-100 TCHO total cholesterol lipids (amino acids peptides and proteins) Protein Binding Research Article lipid absorption Lipoproteins HDL high-density lipoprotein apolipoprotein Diet High-Fat ER endoplasmic reticulum 03 medical and health sciences lipid-binding protein Animals MTTP triglyceride Molecular Biology Triglycerides mouse Lipid Transport 030102 biochemistry & molecular biology Endoplasmic reticulum Biological Transport lipoprotein assembly and secretion Cell Biology Lipid Metabolism CM chylomicron Fatty Liver 030104 developmental biology biology.protein Carrier Proteins Lipoprotein Chylomicron |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.ra120.015002 |
| Popis: | Microsomal triglyceride transfer protein (MTTP) is an endoplasmic reticulum resident protein that is essential for the assembly and secretion of triglyceride (TG)-rich, apoB-containing lipoproteins. Although the function and structure of mammalian MTTP have been extensively studied, how exactly MTTP transfers lipids to lipid acceptors and whether there are other biomolecules involved in MTTP-mediated lipid transport remain elusive. Here we identify a role in this process for the poorly characterized protein PRAP1. We report that PRAP1 and MTTP are partially colocalized in the endoplasmic reticulum. We observe that PRAP1 directly binds to TG and facilitates MTTP-mediated lipid transfer. A single amino acid mutation at position 85 (E85V) impairs PRAP1's ability to form a ternary complex with TG and MTTP, as well as impairs its ability to facilitate MTTP-mediated apoB-containing lipoprotein assembly and secretion, suggesting that the ternary complex formation is required for PRAP1 to facilitate MTTP-mediated lipid transport. PRAP1 is detectable in chylomicron/VLDL-rich plasma fractions, suggesting that MTTP recognizes PRAP1-bound TG as a cargo and transfers TG along with PRAP1 to lipid acceptors. Both PRAP1-deficient and E85V knock-in mutant mice fed a chow diet manifested an increase in the length of their small intestines, likely to compensate for challenges in absorbing lipid. Interestingly, both genetically modified mice gained significantly less body weight and fat mass when on high-fat diets compared with littermate controls and were prevented from hepatosteatosis. Together, this study provides evidence that PRAP1 plays an important role in MTTP-mediated lipid transport and lipid absorption. |
| Databáze: | OpenAIRE |
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