Parkin potentiates ATP-induced currents due to activation of P2X receptors in PC12 cells
| Autor: | Yasuyuki Suzuki, Kumiko Aoki, Yoshimasa Manago, Yukiko Arimura, Mami Noda, Keiji Wada, Ayumi Sato, Taiju Amano, Shunsuke Aoki, Hitoshi Osaka, Etsuko Wada, Mikako Sakurai, Kaori Nishikawa, Rieko Setsuie |
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| Rok vydání: | 2006 |
| Předmět: |
Dopamine and cAMP-Regulated Phosphoprotein 32
Physiology Ubiquitin-Protein Ligases Clinical Biochemistry Transfection Models Biological PC12 Cells Parkin Membrane Potentials Adenosine Triphosphate Ubiquitin Neurotransmitter receptor Ca2+/calmodulin-dependent protein kinase Animals Phosphorylation Protein kinase A Protein kinase C biology Receptors Purinergic P2 Cyclin-dependent kinase 5 Cell Biology Molecular biology nervous system diseases Ubiquitin ligase Cell biology Rats biology.protein alpha-Synuclein Protein Kinases |
| Zdroj: | Journal of cellular physiology. 209(1) |
| ISSN: | 0021-9541 |
| Popis: | 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 alpha-synuclein, a substrate of parkin and also forming Lysine 63-linked multiubiquitin chains. Expression of alpha-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. |
| Databáze: | OpenAIRE |
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