Naa80 acetylates the actin N-terminus impacting the actin cytoskeleton and cell motility

ABSTRACT: Eukaryotic actins undergo several post-translational modifications during their maturation to enable a fully functional cytoskeletal network. A unique N-terminal processing is conserved in the animal kingdom and includes the removal of the first one or two amino acids as well as N-terminal acetylation of the newly exposed acidic N-termini. These events have been known for decades, but the mechanism and function of actin N-terminal acetylation are not well understood due to the lack of information on the catalysing N-terminal acetyltransferase (NAT). Here, we show that NAA80, previously known as NAT6 or FUS-2,is a unique, animal kingdom-specific NAT that exclusively N-terminally acetylates actins. In vitro, the lack of actin N-terminal acetylation impedes the actin polymerization rate due to decreased formin-mediated filament elongation, while the depolymerisation rate is unaffected. Human NAA80 knockout cells display a complete loss of actin N-terminal acetylation and a reorganization of the actin cytoskeleton. We reveal Naa80 as the enzyme that specifically N-terminally acetylates actin the most abundant protein in animal cells, and that this modification controls cellular dynamics and cytoskeletal functions. In this project acetylation of actins was investigated with the use of LC-MS/MS and MS1 quantitation of the Total Ion Current signal.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Haploid Cell

DISEASE(S): Chronic Myeloid Leukemia

SUBMITTER: Evy Timmerman  

LAB HEAD: Thomas Arnesen

PROVIDER: PXD006856 | Pride | 2018-10-24

REPOSITORIES: Pride