Premium
Transient lysine acetylation/deacetylation in the lumen of the ER/Golgi compartments: a novel form of post‐translational modification of nascent membrane proteins
Author(s) -
Puglielli Luigi,
Costantini Claudio,
Kolasani Rekha
Publication year - 2006
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.20.5.a964-d
Subject(s) - acetylation , endoplasmic reticulum , lysine , microbiology and biotechnology , chemistry , protein folding , membrane protein , golgi apparatus , biochemistry , biology , membrane , amino acid , gene
Newly synthesized membrane proteins start folding in the endoplasmic reticulum (ER) while translocating through the ribosome/sec61 complex. The efficiency of folding itself is enhanced through several biochemical events, which include chaperones and enzymes that modify, either temporally or definitively, the protein. We have shown that the lipid second messenger ceramide regulates the molecular stability of the β‐site APP cleaving enzyme 1 (BACE1) (J. Biol. Chem. 2003). Here we report that BACE1 is acetylated in seven different lysine residues clustered around highly disordered regions of the N‐terminal (endolumenal) portion of the nascent protein. This process involves lysine acetylation in the lumen of the ER and is followed by protein deacetylation in the lumen of the Golgi apparatus, once the nascent protein is fully mature. We also show that a dual‐enzymatic machinery acts in the ER and Golgi apparatus respectively to acetylate and deacetylate the lysine residues. In addition, this process requires carrier‐mediated translocation of acetyl‐CoA into the lumen of the ER and is stimulated by ceramide. Site‐directed mutagenesis revealed that the transient lysine acetylation of BACE1 is required for correct exit of the protein from the ER. Finally, we show that the reversible lysine acetylation is not limited to BACE1 but also extended to additional ER resident/transiting proteins, suggesting that it might function as a novel form of post‐translational regulation that controls the molecular stability of ER resident/transiting membrane proteins. Supported by N.I.H.