Potentiation of ATP-induced currents due to the activation of P2X receptors by ubiquitin carboxy-terminal hydrolase L1

Yoshimasa Manago, Yoshiko Kanahori, Aki Shimada, Ayumi Sato, Taiju Amano, Yae Sato-Sano, Rieko Setsuie, Mikako Sakurai, Shunsuke Aoki, Yu Lai Wang, Hitoshi Osaka, Keiji Wada, Mami Noda

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Mammalian neuronal cells abundantly express a de-ubiquitinating isozyme, ubiquitin carboxy-terminal hydrolase L1 (UCH L1). Loss of UCH L1 function causes dying-back type of axonal degeneration. However, the function of UCH L1 in neuronal cells remains elusive. Here we show that overexpression of UCH L1 potentiated ATP-induced currents due to the activation of P2X receptors that are widely distributed in the brain and involved in various biological activities including neurosecretion. ATP-induced inward currents were measured in mock-, wild-type or mutant (C90S)-UCH L1-transfected PC12 cells under the conventional whole-cell patch clamp configuration. The amplitude of ATP-induced currents was significantly greater in both wild-type and C90S UCH L1-transfected cells, suggesting that hydrolase activity was not involved but increased level of mono-ubiquitin might play an important role. The increased currents were dependent on cAMP-dependent protein kinase (PKA) and Ca2+ and calmodulin-dependent protein kinase (CaMKII) but not protein kinase C. In addition, ATP-induced currents were likely to be modified via dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32) that is regulated by PKA and phosphatases. Our finding shows the first evidence that there is a relationship between UCH L1 and neurotransmitter receptor, suggesting that UCH L1 may play an important role in synaptic activity.

Original languageEnglish
Pages (from-to)1061-1072
Number of pages12
JournalJournal of Neurochemistry
Volume92
Issue number5
DOIs
Publication statusPublished - Mar 1 2005

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Ubiquitin Thiolesterase
Induced currents
Adenosine Triphosphate
Chemical activation
Neurosecretion
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Neurotransmitter Receptor
Phosphoprotein Phosphatases
Phosphoproteins
PC12 Cells
Clamping devices
Hydrolases
Ubiquitin
Cyclic AMP-Dependent Protein Kinases
Bioactivity
Cyclic AMP
Protein Kinases
Protein Kinase C
Isoenzymes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Potentiation of ATP-induced currents due to the activation of P2X receptors by ubiquitin carboxy-terminal hydrolase L1. / Manago, Yoshimasa; Kanahori, Yoshiko; Shimada, Aki; Sato, Ayumi; Amano, Taiju; Sato-Sano, Yae; Setsuie, Rieko; Sakurai, Mikako; Aoki, Shunsuke; Wang, Yu Lai; Osaka, Hitoshi; Wada, Keiji; Noda, Mami.

In: Journal of Neurochemistry, Vol. 92, No. 5, 01.03.2005, p. 1061-1072.

Research output: Contribution to journalArticle

Manago, Y, Kanahori, Y, Shimada, A, Sato, A, Amano, T, Sato-Sano, Y, Setsuie, R, Sakurai, M, Aoki, S, Wang, YL, Osaka, H, Wada, K & Noda, M 2005, 'Potentiation of ATP-induced currents due to the activation of P2X receptors by ubiquitin carboxy-terminal hydrolase L1', Journal of Neurochemistry, vol. 92, no. 5, pp. 1061-1072. https://doi.org/10.1111/j.1471-4159.2004.02963.x
Manago, Yoshimasa ; Kanahori, Yoshiko ; Shimada, Aki ; Sato, Ayumi ; Amano, Taiju ; Sato-Sano, Yae ; Setsuie, Rieko ; Sakurai, Mikako ; Aoki, Shunsuke ; Wang, Yu Lai ; Osaka, Hitoshi ; Wada, Keiji ; Noda, Mami. / Potentiation of ATP-induced currents due to the activation of P2X receptors by ubiquitin carboxy-terminal hydrolase L1. In: Journal of Neurochemistry. 2005 ; Vol. 92, No. 5. pp. 1061-1072.
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