An organellar nα-acetyltransferase, naa60, acetylates cytosolic N termini of transmembrane proteins and maintains Golgi integrity

  • Cell Rep. 2015 Mar 3;10(8):1362-74. doi: 10.1016/j.celrep.2015.01.053.
Henriette Aksnes  1 ,  Petra Van Damme  2 ,  Marianne Goris  1 ,  Kristian K Starheim  1 ,  Michaël Marie  1 ,  Svein Isungset Støve  1 ,  Camilla Hoel  1 ,  Thomas Vikestad Kalvik  1 ,  Kristine Hole  3 ,  Nina Glomnes  3 ,  Clemens Furnes  1 ,  Sonja Ljostveit  1 ,  Mathias Ziegler  1 ,  Marc Niere  1 ,  Kris Gevaert  2 ,  Thomas Arnesen  4
Affiliations
  • 1. Department of Molecular Biology, University of Bergen, 5020 Bergen, Norway.
  • 2. Department of Medical Protein Research, VIB, 9000 Ghent, Belgium; Department of Biochemistry, Ghent University, 9000 Ghent, Belgium.
  • 3. Department of Molecular Biology, University of Bergen, 5020 Bergen, Norway; Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.
  • 4. Department of Molecular Biology, University of Bergen, 5020 Bergen, Norway; Department of Surgery, Haukeland University Hospital, 5021 Bergen, Norway. Electronic address: [email protected].
PMID: 25732826 DOI: 10.1016/j.celrep.2015.01.053
Abstract

N-terminal acetylation is a major and vital protein modification catalyzed by N-terminal acetyltransferases (NATs). NatF, or Nα-acetyltransferase 60 (Naa60), was recently identified as a NAT in multicellular eukaryotes. Here, we find that Naa60 differs from all Other known NATs by its Golgi localization. A new membrane topology assay named PROMPT and a selective membrane permeabilization assay established that Naa60 faces the cytosolic side of intracellular membranes. An Nt-acetylome analysis of NAA60-knockdown cells revealed that Naa60, as opposed to Other NATs, specifically acetylates transmembrane proteins and has a preference for N termini facing the cytosol. Moreover, NAA60 knockdown causes Golgi fragmentation, indicating an important role in the maintenance of the Golgi's structural integrity. This work identifies a NAT associated with membranous compartments and establishes N-terminal acetylation as a common modification among transmembrane proteins, a thus-far poorly characterized part of the N-terminal acetylome.