N-acetyltransferase ARD1-NAT1 regulates neuronal dendritic development.
ARD1 and NAT1 constitute an N-acetyltransferase complex where ARD1 holds the enzymatic activity of the complex. The ARD1-NAT1 complex mediates N-terminal acetylation of nascent polypeptides that emerge from ribosomes after translation. ARD1 may also acetylate the internal lysine residues of proteins. Although ARD1 and NAT1 have been found in the brain, the physiological role and substrates of the ARD1-NAT1 complex in neurons remain unclear. Here we investigated role of N-acetyltransferase activity in the process of neuronal development. Expression of ARD1 and NAT1 increased during dendritic development, and both proteins colocalized with microtubules in dendrites. The ARD1-NAT1 complex displayed acetyltransferase activity against a purified microtubule fraction in vitro. Inhibition of the complex limited the dendritic extension of cultured neurons. These findings suggest that the ARD1-NAT1 complex has acetyltransferase activity against microtubules in dendrites. Regulation by acetyltransferase activity is a novel mechanism that is required for dendritic arborization during neuronal development.
Ohkawa
Noriaki
N
Mitsubishi Kagaku Institute of Life Sciences, MITILS, 11 Minamiooya, Machida, Tokyo 194-8511, Japan.
Sugisaki
Shunichiro
S
Tokunaga
Eri
E
Fujitani
Kazuko
K
Hayasaka
Takahiro
T
Setou
Mitsutoshi
M
Inokuchi
Kaoru
K
D000123:Acetyltransferases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D003712:Dendrites / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D063209:N-Terminal Acetyltransferase A; D063213:N-Terminal Acetyltransferase E; D009474:Neurons / Q000201:enzymology* / Q000378:metabolism; D017354:Point Mutation; D051381:Rats; D014162:Transfection
D007527:Isoenzymes; D000123:Acetyltransferases; D063209:N-Terminal Acetyltransferase A; C508558:Naa10 protein, mouse; D063213:N-Terminal Acetyltransferase E; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1