Hepatic TM6SF2 Is Required for Lipidation of VLDL in a Pre-Golgi Compartment in Mice and Rats
Fei Luo, Ēriks Šmagris, Sarah A. Martin, Gonçalo Vale, Jeffrey G. McDonald, Justin A. Fletcher, Shawn C. Burgess, Helen H. Hobbs, Jonathan C. Cohen
Abstract
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.