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

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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
actin, NAA80, NAT, N-terminal acetylation, cell motility, ARP2/3 COMPLEX, YEAST ACTIN, IN-VITRO, ACETYLATION, EVOLUTION, FILAMENTS, FORMINS, CONTRACTION, NUCLEATION, MIGRATION

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Chicago
Drazic, Adrian, Henriette Aksnes, Michaël Marie, Malgorzata Boczkowska, Sylvia Varland, Evy Timmerman, Håvard Foyn, et al. 2018. “NAA80 Is Actin’s N-terminal Acetyltransferase and Regulates Cytoskeleton Assembly and Cell Motility.” Proceedings of the National Academy of Sciences of the United States of America 115 (17): 4399–4404.
APA
Drazic, A., Aksnes, H., Marie, M., Boczkowska, M., Varland, S., Timmerman, E., Foyn, H., et al. (2018). NAA80 is actin’s N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 115(17), 4399–4404.
Vancouver
1.
Drazic A, Aksnes H, Marie M, Boczkowska M, Varland S, Timmerman E, et al. NAA80 is actin’s N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2018;115(17):4399–404.
MLA
Drazic, Adrian, Henriette Aksnes, Michaël Marie, et al. “NAA80 Is Actin’s N-terminal Acetyltransferase and Regulates Cytoskeleton Assembly and Cell Motility.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 115.17 (2018): 4399–4404. Print.
@article{8566359,
  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.},
  author       = {Drazic, Adrian and Aksnes, Henriette and Marie, Micha{\"e}l and Boczkowska, Malgorzata and Varland, Sylvia and Timmerman, Evy and Foyn, H{\aa}vard and Glomnes, Nina and Rebowski, Grzegorz and Impens, Francis and Gevaert, Kris and Dominguez, Roberto and Arnesen, Thomas},
  issn         = {0027-8424},
  journal      = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
  language     = {eng},
  number       = {17},
  pages        = {4399--4404},
  title        = {NAA80 is actin{\textquoteright}s N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility},
  url          = {http://dx.doi.org/10.1073/pnas.1718336115},
  volume       = {115},
  year         = {2018},
}

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