An Organellar Nα-Acetyltransferase, Naa60, Acetylates Cytosolic N Termini of Transmembrane Proteins and Maintains Golgi Integrity

被引:92
作者
Aksnes, Henriette [1 ]
Van Damme, Petra [2 ,3 ]
Goris, Marianne [1 ]
Starheim, Kristian K. [1 ]
Marie, Michael [1 ]
Stove, Svein Isungset [1 ]
Hoel, Camilla [1 ]
Kalvik, Thomas Vikestad [1 ]
Hole, Kristine [1 ,4 ]
Glomnes, Nina [1 ,4 ]
Furnes, Clemens [1 ]
Ljostveit, Sonja [1 ]
Ziegler, Mathias [1 ]
Niere, Marc [1 ]
Gevaert, Kris [2 ,3 ]
Arnesen, Thomas [1 ,5 ]
机构
[1] Univ Bergen, Dept Mol Biol, N-5020 Bergen, Norway
[2] Univ Ghent VIB, Dept Med Prot Res, B-9000 Ghent, Belgium
[3] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium
[4] Univ Bergen, Dept Clin Sci, N-5020 Bergen, Norway
[5] Haukeland Hosp, Dept Surg, N-5021 Bergen, Norway
基金
比利时弗兰德研究基金会;
关键词
SACCHAROMYCES-CEREVISIAE; GTPASE ARL3P; COMPLEX; YEAST; CONSERVATION; MICROTUBULES; ORGANIZATION; INSIGHTS; REQUIRES; SAN;
D O I
10.1016/j.celrep.2015.01.053
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
N-terminal acetylation is a major and vital protein modification catalyzed by N-terminal acetyltransferases (NATs). NatF, or N alpha-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.
引用
收藏
页码:1362 / 1374
页数:13
相关论文
共 37 条
[1]   Towards a Functional Understanding of Protein N-Terminal Acetylation [J].
Arnesen, Thomas .
PLOS BIOLOGY, 2011, 9 (05)
[2]   Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans [J].
Arnesen, Thomas ;
Van Damme, Petra ;
Polevoda, Bogdan ;
Helsens, Kenny ;
Evjenth, Rune ;
Colaert, Niklaas ;
Varhaug, Jan Erik ;
Vandekerckhove, Joel ;
Lillehaug, Johan R. ;
Sherman, Fred ;
Gevaert, Kris .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (20) :8157-8162
[3]   Targeting of the arf-like GTPase Arl3p to the Golgi requires N-terminal acetylation and the membrane protein Sys1p [J].
Behnia, R ;
Panic, B ;
Whyte, JRC ;
Munro, S .
NATURE CELL BIOLOGY, 2004, 6 (05) :405-+
[4]   The yeast orthologue of GRASP65 forms a complex with a coiled-coil protein that contributes to ER to Golgi traffic [J].
Behnia, Rudy ;
Barr, Francis A. ;
Flanagan, John J. ;
Barlowe, Charles ;
Munro, Sean .
JOURNAL OF CELL BIOLOGY, 2007, 176 (03) :255-261
[5]   Genetic modifiers of Drosophila palmitoyl-protein thioesterase 1-induced degeneration [J].
Buff, Haley ;
Smith, Alexis C. ;
Korey, Christopher A. .
GENETICS, 2007, 176 (01) :209-220
[6]   GCN5-related N-acetyltransferases: A structural overview [J].
Dyda, F ;
Klein, DC ;
Hickman, AB .
ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE, 2000, 29 :81-103
[7]   Human Naa50p (Nat5/San) Displays Both Protein Nα- and Nε-Acetyltransferase Activity [J].
Evjenth, Rune ;
Hole, Kristine ;
Karlsen, Odd A. ;
Ziegler, Mathias ;
Arnesen, Thomas ;
Lillehaug, Johan R. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (45) :31122-31129
[8]   N-Terminal Acetylation Inhibits Protein Targeting to the Endoplasmic Reticulum [J].
Forte, Gabriella M. A. ;
Pool, Martin R. ;
Stirling, Colin J. .
PLOS BIOLOGY, 2011, 9 (05)
[9]   The yeast Nα-acetyltransferase NatA is quantitatively anchored to the ribosome and interacts with nascent polypeptides [J].
Gautschi, M ;
Just, S ;
Mun, A ;
Ross, S ;
Rücknagel, P ;
Dubaquié, Y ;
Ehrenhofer-Murray, A ;
Rospert, S .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (20) :7403-7414
[10]   Identification and Functional Characterization of N-Terminally Acetylated Proteins in Drosophila melanogaster [J].
Goetze, Sandra ;
Qeli, Ermir ;
Mosimann, Christian ;
Staes, An ;
Gerrits, Bertran ;
Roschitzki, Bernd ;
Mohanty, Sonali ;
Niederer, Eva M. ;
Laczko, Endre ;
Timmerman, Evy ;
Lange, Vinzenz ;
Hafen, Ernst ;
Aebersold, Ruedi ;
Vandekerckhove, Joel ;
Basler, Konrad ;
Ahrens, Christian H. ;
Gevaert, Kris ;
Brunner, Erich .
PLOS BIOLOGY, 2009, 7 (11)