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

Ayumi Sato, Yukiko Arimura, Yoshimasa Manago, Kaori Nishikawa, Kumiko Aoki, Etsuko Wada, Yasuyuki Suzuki, Hitoshi Osaka, Rieko Setsuie, Mikako Sakurai, Taiju Amano, Shunsuke Aoki, Keiji Wada, Mami Noda

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)172-182
Number of pages11
JournalJournal of cellular physiology
Volume209
Issue number1
DOIs
Publication statusPublished - Oct 1 2006

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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