| RRC ID |
43231
|
| 著者 |
Cen X, Nitta A, Ibi D, Zhao Y, Niwa M, Taguchi K, Hamada M, Ito Y, Ito Y, Wang L, Nabeshima T.
|
| タイトル |
Identification of Piccolo as a regulator of behavioral plasticity and dopamine transporter internalization.
|
| ジャーナル |
Mol Psychiatry
|
| Abstract |
Dopamine transporter (DAT) internalization is a mechanism underlying the decreased dopamine reuptake caused by addictive drugs like methamphetamine (METH). We found that Piccolo, a presynaptic scaffolding protein, was overexpressed in the nucleus accumbens (NAc) of the mice repeatedly administrated with METH. Piccolo downexpression by antisense technique augmented METH-induced behavioral sensitization, conditioned reward and synaptic dopamine accumulation in NAc. Expression of Piccolo C2A domain attenuated METH-induced inhibition of dopamine uptake in PC12 cells expressing human DAT. Consistent with this, it slowed down the accelerated DAT internalization induced by METH, thus maintaining the presentation of plasmalemmal DAT. In immunostaining and structural modeling Piccolo C2A domain displays an unusual feature of sequestering membrane phosphatidylinositol 4,5-bisphosphate, which may underlie its role in modulating DAT internalization. Together, our results indicate that Piccolo upregulation induced by METH represents a homeostatic response in the NAc to excessive dopaminergic transmission. Piccolo C2A domain may act as a cytoskeletal regulator for plasmalemmal DAT internalization, which may underlie its contributions in behavioral plasticity.
|
| 巻・号 |
13(4)
|
| ページ |
349, 451-63
|
| 公開日 |
2008-4-1
|
| DOI |
10.1038/sj.mp.4002132
|
| PII |
4002132
|
| PMID |
18195717
|
| MeSH |
Analysis of Variance
Animals
Behavior, Animal / drug effects
Behavior, Animal / physiology*
Conditioning, Operant / drug effects
Conditioning, Operant / physiology
Cytoskeletal Proteins / physiology*
Dopamine / metabolism
Dopamine Plasma Membrane Transport Proteins / metabolism*
Dopamine Uptake Inhibitors / pharmacology
Humans
Methamphetamine / pharmacology
Mice
Mice, Inbred C57BL
Microdialysis / methods
Motor Activity / drug effects
Neuropeptides / physiology*
Nucleus Accumbens / drug effects
Nucleus Accumbens / metabolism
Oligodeoxyribonucleotides, Antisense / pharmacology
PC12 Cells
Phosphatidylinositol 4,5-Diphosphate / metabolism
Protein Structure, Tertiary
Protein Transport / drug effects
Protein Transport / physiology
Rats
Transfection
|
| IF |
12.384
|
| 引用数 |
27
|
| リソース情報 |
| ヒト・動物細胞 |
PC-12(RCB0009) |
