EGFR SIGNALING UPREGULATES SURFACE EXPRESSION OF THE GluN2B-CONTAINING NMDA RECEPTOR AND CONTRIBUTES TO LONG-TERM POTENTIATION IN THE HIPPOCAMPUS
EGFR SIGNALING UPREGULATES SURFACE EXPRESSION OF THE GluN2B-CONTAINING NMDA RECEPTOR AND CONTRIBUTES TO LONG-TERM POTENTIATION IN THE HIPPOCAMPUS
复制标题
EGFR 信号传导上调含有 GluN2B 的 NMDA 受体的表面表达并有助于海马体的长期增强
DOI：
10.1016/j.neuroscience.2015.07.021
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发表时间：
2015-09
期刊：
影响因子：
3.3
通讯作者：
Luo J.
中科院分区：
文献类型：
--
作者：
Tang Y.;Ye M.;Du Y.;Qiu X.;Lv X.;Yang W.;Luo J.
N-甲基-d-天冬氨酸受体(NMDAR)受多种受体酪氨酸激酶的调节。表皮生长因子受体(EGFR)的激活特异性地增加了NMDAR介导的电流并增强了海马区的长时程增强(LTP)。然而，EGFR调控NMDARs的机制仍有待阐明。在本研究中，我们发现EGFR在海马区高表达，并且主要定位于非突触区域，包括培养的海马神经元的胞体和突起。EGFR激活导致对异丙苯地尔敏感的NMDAR电流增加。与此一致，我们还观察到含有GluN2B的NMDAR的表面表达上调。我们的海马片和培养的海马神经元的生化数据表明，EGF处理后，Y1472的GluN2B亚基的磷酸化显著增加，同时伴随着Src家族激酶(SFK)的激活。用特异性拮抗剂BIBX-1382阻断EGFR可减弱高频刺激(HFS)诱导的LTP突触后密度GluN2B的增加。此外，阻断BIBX可显著减弱HFS诱导的LTP。总之，我们的发现表明，EGFR信号通过修改GluN2B亚基上调NMDAR，这是HFS诱导的海马区LTP所必需的。
N-methyl-d-aspartate receptors (NMDARs) have been known to be regulated by various receptor tyrosine kinases. Activation of epidermal growth factor receptor (EGFR) specifically increases NMDAR-mediated currents and enhances long-term potentiation (LTP) in the hippocampus. However, the mechanism through which EGFR regulates NMDARs remains to be elucidated. In this study we found that EGFR was highly expressed in the hippocampus and mainly localized in the non-synaptic region including the soma and neurites of cultured hippocampal neurons. EGFR activation led to an increase in ifenprodil-sensitive NMDAR currents. Consistent with this, we also observed that surface expression of GluN2B-containing NMDAR was upregulated. Our biochemical data from hippocampal slices and hippocampal cultured neurons demonstrated that EGF treatmentin vitrosignificantly increased phosphorylation of the GluN2B subunit at Y1472 with a coincidental activation of Src family kinases (SFKs). EGFR blockade with a specific antagonist BIBX-1382 attenuated an increase of GluN2B in the postsynaptic density during high-frequency stimulation (HFS)-induced LTP. Moreover, BIBX blockade significantly impaired HFS-induced LTP. In conclusion, our findings suggest that EGFR signaling upregulates NMDARs through modification of the GluN2B subunit, and is required for HFS-induced LTP in the hippocampus.
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DOI：
10.1073/pnas.89.10.4363
发表时间：
1992-05-15
影响因子：
11.1
作者：
DUDEK, SM;BEAR, MF
通讯作者：
BEAR, MF
影响因子：
25
作者：
F. Zheng;M. B. Gingrich;S. Traynelis;P. Conn
通讯作者：
F. Zheng;M. B. Gingrich;S. Traynelis;P. Conn
影响因子：
16.2
作者：
Huang, YZ;Won, S;Mei, L
通讯作者：
Mei, L
DOI：
--
发表时间：
2007
影响因子：
11.1
作者：
H. Man;Y. Sekine‐Aizawa;R. Huganir
通讯作者：
H. Man;Y. Sekine‐Aizawa;R. Huganir
影响因子：
64.5
作者：
Dalva, MB;Takasu, MA;Greenberg, ME
通讯作者：
Greenberg, ME