2. Academic Validation
  3. A critical role of VMP1 in lipoprotein secretion

A critical role of VMP1 in lipoprotein secretion

  • Elife. 2019 Sep 17;8:e48834. doi: 10.7554/eLife.48834.
Hideaki Morishita 1,  Yan G Zhao # 2 3,  Norito Tamura # 1,  Taki Nishimura 1,  Yuki Kanda 1,  Yuriko Sakamaki 4,  Mitsuyo Okazaki 5,  Dongfang Li 2,  Noboru Mizushima 1
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, University of Tokyo, Tokyo, Japan.
  • 2 National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • 3 Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States.
  • 4 Microscopy Research Support Unit Research Core, Tokyo Medical and Dental University, Tokyo, Japan.
  • 5 Tokyo Medical and Dental University, Tokyo, Japan.
  • # Contributed equally.
PMID: 31526472 DOI: 10.7554/eLife.48834
Abstract

Lipoproteins are lipid-protein complexes that are primarily generated and secreted from the intestine, liver, and visceral endoderm and delivered to peripheral tissues. Lipoproteins, which are assembled in the endoplasmic reticulum (ER) membrane, are released into the ER lumen for secretion, but its mechanism remains largely unknown. Here, we show that the release of lipoproteins from the ER membrane requires VMP1, an ER transmembrane protein essential for Autophagy and certain types of secretion. Loss of vmp1, but not Other autophagy-related genes, in zebrafish causes lipoprotein accumulation in the intestine and liver. Vmp1 deficiency in mice also leads to lipid accumulation in the visceral endoderm and intestine. In VMP1-depleted cells, neutral lipids accumulate within lipid bilayers of the ER membrane, thus affecting lipoprotein secretion. These results suggest that VMP1 is important for the release of lipoproteins from the ER membrane to the ER lumen in addition to its previously known functions.

Keywords

VMP1; autophagy-related gene; cell biology; endoplasmic reticulum; human; lipoprotein; mouse; zebrafish.

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