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bioRxiv · 10.1101/2025.05.07.651779

NT5DC2 downregulation suppresses monoamine oxidase activity and increases catecholamine levels in PC12D cells

Yamaguchi, H.·Kawata, M.·Kodani, Y.·Saito, K.·Kameyama, T.·Nagasaki, H.·Nakashima, A.
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Abstract

Back groundGenome-wide association studies have revealed the involvement of 5-nucleotidase domain-containing protein 2 (NT5DC2) in neuropsychiatric disorders such as schizophrenia and bipolar disorder; however, its function remains unclear. Recently, we found that NT5DC2 downregulation in PC12D cells increases catecholamine synthesis by promoting the activity of tyrosine hydroxylase and that monoamine oxidase A (MAO A) might bind to NT5DC2 using Affinity Purification-Mass Spectroscopy. Methods and ResultsWe investigated the role of NT5DC2 for MAO A activity in PC12D cells. Western blot analysis revealed that NT5DC2 primarily binds to the non-phosphorylated form of MAO A. siRNA-mediated NT5DC2 downregulation reduced MAO A activity, leading to decreased dopamine metabolism and increased noradrenaline synthesis. ConclusionOur findings suggest that NT5DC2 could affect both tyrosine hydroxylase and MAO A activity to control catecholamine synthesis. Therefore, our study provides valuable insights into disorders associated with catecholamine dysregulation, such as Parkinsons disease and neuropsychiatric disorders.

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Yamaguchi, H., Kawata, M., Kodani, Y., Saito, K., Kameyama, T., Nagasaki, H., Nakashima, A.. 2025-05-10. NT5DC2 downregulation suppresses monoamine oxidase activity and increases catecholamine levels in PC12D cells. https://doi.org/10.1101/2025.05.07.651779

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