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PRAP1 is a novel lipid-binding protein that promotes lipid absorption by facilitating MTTP-mediated lipid transport.
Peng, Hubert; Chiu, Tzu-Yuan; Liang, Yu-Jen; Lee, Chia-Jen; Liu, Chih-Syuan; Suen, Ching-Shu; Yen, Jeffrey J-Y; Chen, Hung-Ta; Hwang, Ming-Jing; Hussain, M Mahmood; Yang, Hsin-Chou; Yang-Yen, Hsin-Fang.
Afiliación
  • Peng H; Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
  • Chiu TY; Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
  • Liang YJ; Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
  • Lee CJ; Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
  • Liu CS; Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
  • Suen CS; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • Yen JJ; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • Chen HT; Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
  • Hwang MJ; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • Hussain MM; Foundations of Medicine, NYU Long Island School of Medicine, Mineola, New York, USA.
  • Yang HC; Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
  • Yang-Yen HF; Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan. Electronic address: imbyy@gate.sinica.edu.tw.
J Biol Chem ; 296: 100052, 2021.
Article en En | MEDLINE | ID: mdl-33168624
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Gestacionales / Proteínas Portadoras / Metabolismo de los Lípidos Límite: Animals Idioma: En Revista: J Biol Chem Año: 2021 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Gestacionales / Proteínas Portadoras / Metabolismo de los Lípidos Límite: Animals Idioma: En Revista: J Biol Chem Año: 2021 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos