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


ABSTRACT: 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.

SUBMITTER: Saegusa K 

PROVIDER: S-EPMC5987718 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Saegusa Keiko K   Sato Miyuki M   Morooka Nobukatsu N   Hara Taichi T   Sato Ken K  

The Journal of cell biology 20180411 6


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 <i>Caenorhabditis elegans</i> 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 pre  ...[more]

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