共 35 条
Neuronal activity regulates phosphorylation-dependent surface delivery of G protein-activated inwardly rectifying potassium channels
被引:85
作者:
Chung, Hee Jung
[1
]
Qian, Xiang
[1
]
Ehlers, Melissa
[1
]
Jan, Yuh Nung
[1
]
Jan, Lily Yeh
[1
]
机构:
[1] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94158 USA
来源:
基金:
美国国家卫生研究院;
关键词:
GIRK;
NMDA receptor;
trafficking;
protein phosphatase-1;
dendrites;
RECTIFIER K+ CHANNELS;
HIPPOCAMPAL PYRAMIDAL CELLS;
SUBCELLULAR-LOCALIZATION;
PLASMA-MEMBRANE;
RAT HIPPOCAMPUS;
RECEPTORS;
TRAFFICKING;
DENDRITES;
ENDOSOMES;
PHOSPHATASE-1;
D O I:
10.1073/pnas.0811615106
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
G protein-activated inwardly rectifying K+ (GIRK) channels regulate neuronal excitability by mediating inhibitory effects of G protein-coupled receptors for neurotransmitters and neuromodulators. Notwithstanding many studies reporting modulation of GIRK channel function, whether neuronal activity regulates GIRK channel trafficking remains an open question. Here we report that NMDA receptor activation in cultured dissociated hippocampal neurons elevates surface expression of the GIRK channel subunits GIRK1 and GIRK2 in the soma, dendrites, and dendritic spines within 15 min. This activity-induced increase in GIRK surface expression requires protein phosphatase-1-mediated dephosphorylation of a serine residue (Ser-9) preceding the GIRK2 Val-13/Leu-14 (VL) internalization motif, thereby promoting channel recycling. Because activation of GIRK channels hyperpolarizes neuronal membranes, the NMDA receptor-induced regulation of GIRK channel trafficking may represent a dynamic adjustment of neuronal excitability in response to inhibitory neurotransmitters and/or neuromodulators.
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页码:629 / 634
页数:6
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