PMID- 16826604
OWN - NLM
STAT- MEDLINE
DCOM- 20061020
LR  - 20161124
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 209
IP  - 1
DP  - 2006 Oct
TI  - Parkin potentiates ATP-induced currents due to activation of P2X receptors in 
      PC12 cells.
PG  - 172-82
AB  - 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.
CI  - Copyright 2006 Wiley-Liss, Inc.
FAU - Sato, Ayumi
AU  - Sato A
AD  - Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Arimura, Yukiko
AU  - Arimura Y
FAU - Manago, Yoshimasa
AU  - Manago Y
FAU - Nishikawa, Kaori
AU  - Nishikawa K
FAU - Aoki, Kumiko
AU  - Aoki K
FAU - Wada, Etsuko
AU  - Wada E
FAU - Suzuki, Yasuyuki
AU  - Suzuki Y
FAU - Osaka, Hitoshi
AU  - Osaka H
FAU - Setsuie, Rieko
AU  - Setsuie R
FAU - Sakurai, Mikako
AU  - Sakurai M
FAU - Amano, Taiju
AU  - Amano T
FAU - Aoki, Shunsuke
AU  - Aoki S
FAU - Wada, Keiji
AU  - Wada K
FAU - Noda, Mami
AU  - Noda M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Dopamine and cAMP-Regulated Phosphoprotein 32)
RN  - 0 (PPP1R1B protein, human)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (SNCA protein, human)
RN  - 0 (Ubiquitin)
RN  - 0 (alpha-Synuclein)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (parkin protein)
RN  - EC 2.7.- (Protein Kinases)
SB  - IM
MH  - Adenosine Triphosphate/*pharmacology
MH  - Animals
MH  - Dopamine and cAMP-Regulated Phosphoprotein 32/metabolism/physiology
MH  - Membrane Potentials/*drug effects
MH  - Models, Biological
MH  - PC12 Cells
MH  - Phosphorylation
MH  - Protein Kinases/metabolism
MH  - Rats
MH  - Receptors, Purinergic P2/*metabolism
MH  - Transfection
MH  - Ubiquitin/*metabolism
MH  - Ubiquitin-Protein Ligases/genetics/metabolism/*physiology
MH  - alpha-Synuclein/physiology
EDAT- 2006/07/11 09:00
MHDA- 2006/10/21 09:00
CRDT- 2006/07/11 09:00
PHST- 2006/07/11 09:00 [pubmed]
PHST- 2006/10/21 09:00 [medline]
PHST- 2006/07/11 09:00 [entrez]
AID - 10.1002/jcp.20719 [doi]
PST - ppublish
SO  - J Cell Physiol. 2006 Oct;209(1):172-82. doi: 10.1002/jcp.20719.