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Related Experiment Videos

An evolutionarily conserved N-terminal acetyltransferase complex associated with neuronal development.

Naoaki Sugiura1, Suzanne M Adams, Roderick A Corriveau

  • 1Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.

The Journal of Biological Chemistry
|July 31, 2003
PubMed
Summary
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Murine N-terminal acetyltransferase 1 (mNAT1) and mARD1 form a functional enzyme complex crucial for neuron development. Their expression and down-regulation are linked to cell division, migration, and differentiation in the developing brain.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • mNAT1 (murine N-terminal acetyltransferase 1) is an embryonic gene in the developing brain.
  • Its down-regulation is linked to N-methyl-d-aspartate (NMDA) receptor function.
  • Mammalian homologues of yeast NAT1, including mNAT1 and mNAT2, were identified, but their function as acetyltransferases was unclear.

Purpose of the Study:

  • To investigate the function of mNAT1 and its co-subunit mARD1.
  • To determine if mNAT1 and mARD1 form a functional acetyltransferase complex.
  • To elucidate the role of this complex in brain development and neuronal differentiation.

Main Methods:

  • Biochemical analysis to assess acetyltransferase activity.
  • Mammalian cell transfection with mNAT1 and mARD1.

Related Experiment Videos

  • Immunofluorescent staining to determine protein localization.
  • In situ hybridization to analyze gene expression patterns in the brain.
  • Studies using P19 embryonic carcinoma cells treated with retinoic acid.

    • Main Results:

    • mNAT1 and its co-subunit mARD1 assemble into a functional N-terminal acetyltransferase.
    • These proteins localize to the cytoplasm in mammalian cells.
    • mNAT1 and mARD1 are highly expressed in dividing and migrating brain cells and down-regulated during neuronal differentiation.
    • Expression of mNAT1 and mARD1 decreases as neurons differentiate in P19 cells, coinciding with NMDA receptor 1 gene induction.

    Conclusions:

    • Vertebrate homologues of NAT1 and ARD1 form an evolutionarily conserved N-terminal acetyltransferase.
    • The expression and down-regulation of this enzyme complex are critical for neuronal generation and differentiation.
    • This study provides the first direct evidence for the functional significance of NAT1/ARD1 in vertebrate brain development.