Parkin potentiates ATP-induced currents due to activation of P2X receptors in PC12 cells

Authors

  • Ayumi Sato,

    1. Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
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  • Yukiko Arimura,

    1. Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
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  • Yoshimasa Manago,

    1. Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
    Current affiliation:
    1. Foods and Fine Chemicals Department, Products Development Section, Maruha Corporation, Tochigi 321-3231, Japan.
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  • Kaori Nishikawa,

    1. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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  • Kumiko Aoki,

    1. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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  • Etsuko Wada,

    1. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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  • Yasuyuki Suzuki,

    1. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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  • Hitoshi Osaka,

    1. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
    2. Information and Cellular Function, PRESTO, Japan Science and Technology Corporation (JST), Kawaguchi, Saitama, Japan
    Current affiliation:
    1. Division of Neurology, Clinical Research Institute, Kanagawa, Children's Medical Center, Yokohama, 232-8555, Japan.
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  • Rieko Setsuie,

    1. Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
    2. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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  • Mikako Sakurai,

    1. Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
    2. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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  • Taiju Amano,

    1. Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
    2. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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  • Shunsuke Aoki,

    1. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
    2. NEDO (New Energy and Industrial Technology Development Organization), Kawasaki, Kanagawa, Japan
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  • Keiji Wada,

    1. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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  • Mami Noda

    Corresponding author
    1. Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
    • Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
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  • Ayumi Sato and Yukiko Arimura contributed equally to this work.

Abstract

Loss-of-function mutations of the parkin gene causes an autosomal recessive juvenile-onset form of Parkinson's disease (AR-JP). Parkin was shown to function as a RING-type E3 ubiquitin protein ligase. However, the function of parkin in neuronal cells remains elusive. Here, we show that expression of parkin-potentiated adenosine triphosphate (ATP)-induced currents that result from activation of the P2X receptors which are widely distributed in the brain and involved in neurotransmission. ATP-induced inward currents were measured in mock-, wild-type or mutant (T415N)-parkin-transfected PC12 cells under the conventional whole-cell patch clamp configuration. The amplitude of ATP-induced currents was significantly greater in wild-type parkin-transfected cells. However, the immunocytochemical study showed no apparent increase in the number of P2X receptors or in ubiquitin levels. The increased currents were attenuated by inhibition of cAMP-dependent protein kinase (PKA) but not protein kinase C (PKC) or Ca2+ and calmodulin-dependent protein kinase (CaMKII). ATP-induced currents were also regulated by phosphatases and cyclin-dependent protein kinase 5 (CDK5) via dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32), though the phosphorylation at Thr-34 and Thr-75 were unchanged or rather attenuated. We also tried to investigate the effect of α-synuclein, a substrate of parkin and also forming Lysine 63-linked multiubiquitin chains. Expression of α-synuclein did not affect the amplitude of ATP-induced currents. Our finding provides the evidence for a relationship between parkin and a neurotransmitter receptor, suggesting that parkin may play an important role in synaptic activity. J. Cell. Physiol. 209: 172–182, 2006. © 2006 Wiley-Liss, Inc.

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