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AT‐1 is an ER membrane acetylCoA transporter and is required for the lysine acetylation of nascent membrane proteins in the ER/ERGIC system
Author(s) -
Jonas Mary Cabell,
Puglielli Luigi
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.605.3
Subject(s) - endoplasmic reticulum , acetylation , chemistry , lysine , golgi apparatus , membrane protein , biochemistry , calnexin , microbiology and biotechnology , membrane , biology , amino acid , calreticulin , gene
Folding of newly synthesized membrane proteins in the endoplasmic reticulum (ER) is enhanced by enzymes that modify, either temporally or definitively, the protein. Our group has shown that the lipid second messenger ceramide regulates the molecular stability of the β‐site APP cleaving enzyme 1 (BACE1) by affecting a transient form of lysine acetylation in the ER/Golgi system (Biochem J 2007; EMBO J 2006; J Biol Chem 2003). Specifically, nascent BACE1 is initially acetylated in the lumen of the ER and then deacetylated by a Golgi‐based deacetylase. The apparent limiting factor in the above events is the translocation of acetylCoA, the donor of the acetyl group in the reaction of acetylation, from the cytoplasm to the lumen of the ER. Here we report the functional identification of AT‐1, a putative acetylCoA membrane transporter that is up‐regulated as result of ER‐induced stress. Biochemical fractionation studies indicated that AT‐1 is enriched in the ER membrane and overlaps with the endogenous acetylCoA membrane transport activity. In addition, ER fractions from AT‐1 expressing cells display increased acetylCoA membrane transport activity, which is inhibited by CoA suggesting an antiporter mechanism. Finally, overexpression of AT‐1 resulted in increased acetylation and steady‐state levels of BACE1. In conclusion, our results indicate that AT‐1 is an ER‐resident acetylCoA membrane transporter.