| First Author | Unoki T | Year | 2012 |
| Journal | Neuron | Volume | 73 |
| Issue | 1 | Pages | 135-48 |
| PubMed ID | 22243752 | Mgi Jnum | J:263428 |
| Mgi Id | MGI:6189392 | Doi | 10.1016/j.neuron.2011.09.034 |
| Citation | Unoki T, et al. (2012) NMDA receptor-mediated PIP5K activation to produce PI(4,5)P(2) is essential for AMPA receptor endocytosis during LTD. Neuron 73(1):135-48 |
| abstractText | 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 Ca(2)(+) influx through the NMDA receptor activates calcineurin and protein phosphatase 1 to dephosphorylate phosphatidylinositol 4-phosphate 5-kinasegamma661 (PIP5Kgamma661), the major phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2))-producing enzyme in the brain. Bimolecular fluorescence complementation analysis revealed that the dephosphorylated PIP5Kgamma661 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 PIP5Kgamma661 and AP-2 and by overexpression of a kinase-dead PIP5Kgamma661 mutant in hippocampal neurons. Furthermore, knockdown of PIP5Kgamma661 inhibited the NMDA-induced AMPA receptor endocytosis. Therefore, NMDA receptor activation controls AMPA receptor endocytosis during hippocampal LTD by regulating PIP5Kgamma661 activity at postsynapses. |
