Hepatic TM6SF2 Is Required for Lipidation of VLDL in a Pre-Golgi Compartment in Mice and Rats

Authors: Fei Luo, Ēriks Šmagris, Sarah A. Martin, Gonçalo Vale, Jeffrey G. McDonald, Justin A. Fletcher, Shawn C. Burgess, Helen H. Hobbs, Jonathan C. Cohen - Cellular and Molecular Gastroenterology and Hepatology 2021 cited by 109

BACKGROUND & AIMS: rats to determine the subcellular location and function of TM6SF2. METHODS: mice and in their wild-type littermates. The intracellular location of TM6SF2 was determined by cell fractionation. Finally, TM6SF2 was immunoprecipitated from liver and enterocytes to identify interacting proteins. RESULTS: mice. TM6SF2 was present predominantly in the smooth endoplasmic reticulum and endoplasmic reticulum-Golgi intermediate compartments, but not in Golgi. Both apolipoprotein B-48 and acyl-CoA synthetase long chain family member 5 physically interacted with TM6SF2. CONCLUSIONS: TM6SF2 acts in the smooth endoplasmic reticulum to promote bulk lipidation of apolipoprotein B-containing lipoproteins, thus preventing fatty liver disease.