2. Academic Validation
  3. NAA80 is actin's N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility

NAA80 is actin's N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility

  • Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4399-4404. doi: 10.1073/pnas.1718336115.
Adrian Drazic 1 2,  Henriette Aksnes 1 2,  Michaël Marie 1 2,  Malgorzata Boczkowska 3,  Sylvia Varland 1 2,  Evy Timmerman 4 5 6,  Håvard Foyn 1,  Nina Glomnes 1 7,  Grzegorz Rebowski 3,  Francis Impens 4 5 6,  Kris Gevaert 4 6,  Roberto Dominguez 3,  Thomas Arnesen 8 2 9
Affiliations

Affiliations

  • 1 Department of Biological Sciences, University of Bergen, N-5020 Bergen, Norway.
  • 2 Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway.
  • 3 Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • 4 Flanders Institute for Biotechnology-Ghent University Center for Medical Biotechnology, B-9000 Ghent, Belgium.
  • 5 Flanders Institute for Biotechnology Proteomics Core, B-9000 Ghent, Belgium.
  • 6 Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium.
  • 7 Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway.
  • 8 Department of Biological Sciences, University of Bergen, N-5020 Bergen, Norway; thomas.arnesen@uib.no.
  • 9 Department of Surgery, Haukeland University Hospital, N-5021 Bergen, Norway.
PMID: 29581253 DOI: 10.1073/pnas.1718336115
Abstract

Actin, one of the most abundant proteins in nature, participates in countless cellular functions ranging from organelle trafficking and pathogen motility to cell migration and regulation of gene transcription. Actin's cellular activities depend on the dynamic transition between its monomeric and filamentous forms, a process exquisitely regulated in cells by a large number of actin-binding and signaling proteins. Additionally, several posttranslational modifications control the cellular functions of actin, including most notably N-terminal (Nt)-acetylation, a prevalent modification throughout the animal kingdom. However, the biological role and mechanism of actin Nt-acetylation are poorly understood, and the identity of actin's N-terminal acetyltransferase (NAT) has remained a mystery. Here, we reveal that NAA80, a suggested NAT Enzyme whose substrate specificity had not been characterized, is Nt-acetylating actin. We further show that actin Nt-acetylation plays crucial roles in cytoskeletal assembly in vitro and in cells. The absence of Nt-acetylation leads to significant differences in the rates of actin filament depolymerization and elongation, including elongation driven by formins, whereas filament nucleation by the Arp2/3 complex is mostly unaffected. NAA80-knockout cells display severely altered cytoskeletal organization, including an increase in the ratio of filamentous to globular actin, increased filopodia and lamellipodia formation, and accelerated cell motility. Together, the results demonstrate NAA80's role as actin's NAT and reveal a crucial role for actin Nt-acetylation in the control of Cytoskeleton structure and dynamics.

Keywords

N-terminal acetylation; NAA80; NAT; actin; cell motility.

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