PRAP1 is a novel lipid-binding protein that promotes lipid absorption by facilitating MTTP-mediated lipid transport

• DOI: 10.1074/jbc.ra120.015002
• Publication Date: 2020-11-10T01:45:22Z
• Authors: Hubert Peng; Tzu-Yuan Chiu; Yu-Jen Liang; Chia-Jen Lee; Chih-Syuan Liu; Ching-Shu Suen; Jeffrey J.-Y. Yen; Hung-Ta Chen; Ming-Jing Hwang; M. Mahmood Hussain; Hsin-Chou Yang; Hsin-Fang Yang-Yen
• Keywords: Chylomicron

Microsomal triglyceride transfer protein (MTTP) is an endoplasmic reticulum resident that essential for the assembly and secretion of (TG)-rich, apoB-containing lipoproteins. Although function structure mammalian MTTP have been extensively studied, how exactly transfers lipids to lipid acceptors whether there are other biomolecules involved in MTTP-mediated transport remain elusive. Here we identify a role this process poorly characterized PRAP1. We report PRAP1 partially colocalized reticulum. observe directly binds TG facilitates transfer. A single amino acid mutation at position 85 (E85V) impairs PRAP1's ability form ternary complex with MTTP, as well its facilitate lipoprotein secretion, suggesting formation required transport. detectable chylomicron/VLDL-rich plasma fractions, recognizes PRAP1-bound cargo along acceptors. Both PRAP1-deficient E85V knock-in mutant mice fed chow diet manifested increase length their small intestines, likely compensate challenges absorbing lipid. Interestingly, both genetically modified gained significantly less body weight fat mass when on high-fat diets compared littermate controls were prevented from hepatosteatosis. Together, study provides evidence plays important absorption.