SFT-4/Surf4 control ER export of soluble cargo proteins and participate in ER exit site organization

J Cell Biol. 2018 Jun 4;217(6):2073-2085. doi: 10.1083/jcb.201708115. Epub 2018 Apr 11.


Lipoproteins regulate the overall lipid homeostasis in animals. However, the molecular mechanisms underlying lipoprotein trafficking remain poorly understood. Here, we show that SFT-4, a Caenorhabditis elegans homologue of the yeast Erv29p, is essential for the endoplasmic reticulum (ER) export of the yolk protein VIT-2, which is synthesized as a lipoprotein complex. SFT-4 loss strongly inhibits the ER exit of yolk proteins and certain soluble cargo proteins in intestinal cells. SFT-4 predominantly localizes at ER exit sites (ERES) and physically interacts with VIT-2 in vivo, which suggests that SFT-4 promotes the ER export of soluble proteins as a cargo receptor. Notably, Surf4, a mammalian SFT-4 homologue, physically interacts with apolipoprotein B, a very-low-density lipoprotein core protein, and its loss causes ER accumulation of apolipoprotein B in human hepatic HepG2 cells. Interestingly, loss of SFT-4 and Surf4 reduced the number of COPII-positive ERES. Thus, SFT-4 and Surf4 regulate the export of soluble proteins, including lipoproteins, from the ER and participate in ERES organization in animals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans / ultrastructure
  • Caenorhabditis elegans Proteins / metabolism*
  • Egg Proteins / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / ultrastructure
  • Hep G2 Cells
  • Humans
  • Intestines / ultrastructure
  • Membrane Proteins / metabolism*
  • Protein Binding
  • Protein Transport
  • RNA Interference
  • Solubility


  • Caenorhabditis elegans Proteins
  • Egg Proteins
  • Membrane Proteins
  • SURF4 protein, human
  • sft-4 protein, C elegans