RRC ID |
28594
|
著者 |
Unoki T, Matsuda S, Kakegawa W, Van NT, Kohda K, Suzuki A, Funakoshi Y, Hasegawa H, Yuzaki M, Kanaho Y.
|
タイトル |
NMDA receptor-mediated PIP5K activation to produce PI(4,5)P₂ is essential for AMPA receptor endocytosis during LTD.
|
ジャーナル |
Neuron
|
Abstract |
NMDA receptor activation leads to clathrin-dependent endocytosis of postsynaptic AMPA receptors. Although this process controls long-term depression (LTD) induction in the hippocampus, how it is regulated by neuronal activities is not completely clear. Here, we show that Ca²⁺ influx through the NMDA receptor activates calcineurin and protein phosphatase 1 to dephosphorylate phosphatidylinositol 4-phosphate 5-kinaseγ661 (PIP5Kγ661), the major phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂)-producing enzyme in the brain. Bimolecular fluorescence complementation analysis revealed that the dephosphorylated PIP5Kγ661 became associated with the clathrin adaptor protein complex AP-2 at postsynapses in situ. NMDA-induced AMPA receptor endocytosis and low-frequency stimulation-induced LTD were completely blocked by inhibiting the association between dephosphorylated PIP5Kγ661 and AP-2 and by overexpression of a kinase-dead PIP5Kγ661 mutant in hippocampal neurons. Furthermore, knockdown of PIP5Kγ661 inhibited the NMDA-induced AMPA receptor endocytosis. Therefore, NMDA receptor activation controls AMPA receptor endocytosis during hippocampal LTD by regulating PIP5Kγ661 activity at postsynapses.
|
巻・号 |
73(1)
|
ページ |
135-48
|
公開日 |
2012-1-12
|
DOI |
10.1016/j.neuron.2011.09.034
|
PII |
S0896-6273(11)00925-1
|
PMID |
22243752
|
MeSH |
Actins / metabolism
Adaptor Protein Complex 2 / metabolism
Animals
Animals, Newborn
Biophysics
Cells, Cultured
Disks Large Homolog 4 Protein
Dose-Response Relationship, Drug
Electric Stimulation
Embryo, Mammalian
Endocytosis / drug effects
Endocytosis / genetics
Endocytosis / physiology*
Enzyme Inhibitors / pharmacology
Excitatory Amino Acid Agonists / pharmacology
Gene Expression Regulation / drug effects
Gene Expression Regulation / genetics
Green Fluorescent Proteins / genetics
Guanylate Kinases / metabolism
Hippocampus / cytology
Immunoprecipitation
In Vitro Techniques
Long-Term Synaptic Depression / drug effects
Long-Term Synaptic Depression / genetics
Long-Term Synaptic Depression / physiology*
Membrane Proteins / metabolism
Mice
Mice, Inbred ICR
Mutation / genetics
N-Methylaspartate / pharmacology
Nerve Tissue Proteins / metabolism
Neurons / drug effects
Neurons / physiology*
Patch-Clamp Techniques
Phosphotransferases (Alcohol Group Acceptor) / genetics
Phosphotransferases (Alcohol Group Acceptor) / metabolism*
Protein Transport / drug effects
Protein Transport / genetics
RNA, Small Interfering
Receptors, AMPA / genetics
Receptors, AMPA / metabolism*
Receptors, N-Methyl-D-Aspartate / metabolism
Time Factors
Transfection
|
IF |
14.415
|
引用数 |
45
|
WOS 分野
|
NEUROSCIENCES
|
リソース情報 |
遺伝子材料 |
pGEX6P1- PIP5Kc661 Cterm-WT(434-661 a.a.) (RDB08477)
pGEX6P1- PIP5Kc661 Cterm-SA(434-661 a.a.) (RDB08478)
pGEX6P1- PIP5Kc661 Cterm-SE(434-661 a.a.) (RDB08479)
pGEX6P1- PIP5Kc661 C26aa-SA(636-661 a.a.) (RDB08480)
pGEX6P1- PIP5Kc661 C26aa-SE(636-661 a.a.) (RDB08481) |