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

研究成果: ジャーナルへの寄稿学術誌査読

15 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)1061-1072
ページ数12
ジャーナルJournal of Neurochemistry
92
5
DOI
出版ステータス出版済み - 3月 2005
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 細胞および分子神経科学

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