2012年10月31日 訊 /生物谷BIOON/ --近日，喬治亞州佐治亞州健康科學(xué)大學(xué)醫(yī)學(xué)院神經(jīng)科學(xué)家證實(shí)兩種蛋白質(zhì)的結(jié)合能使對學(xué)習(xí)和記憶至關(guān)重要的大腦受體不僅獲得表達(dá),，同時也有助保持這些受體保留在所需要的地方,。
NMDA受體能增加腦細(xì)胞的活性和腦細(xì)胞之間的交流，NMDA受體就像一個接收端,，在腦細(xì)胞交流中發(fā)揮關(guān)鍵作用,。在腦退化疾病如阿爾茨海默氏病和帕金森氏癥中，NMDA受體是治療靶點(diǎn),。
研究人員已經(jīng)發(fā)現(xiàn)有助于穩(wěn)定細(xì)胞表面受體的支架蛋白(scaffolding protein)SAP102,，結(jié)合NMDA受體亞單位GluN2B兩個位點(diǎn)。佐治亞州健康科學(xué)大學(xué)醫(yī)學(xué)院的喬治亞州的神經(jīng)科學(xué)家Bo-Shiun Chen表示：一個結(jié)合位點(diǎn)參與穩(wěn)定細(xì)胞表面上的受體,，另一個位點(diǎn)在清除受體中是很重要的,。以前，研究人員從來沒有想過相同的支架蛋白會有兩個角色,，相關(guān)研究結(jié)果發(fā)表在Cell Reports雜志上,。
科學(xué)家相信通過了解這些受體功能的正常轉(zhuǎn)化，可以更多了解如何防止如老年癡呆癥等疾病,。有趣的是,，這個關(guān)鍵蛋白質(zhì)SAP102,，是骨架蛋白MAGUK家庭成員中唯一直接促發(fā)疾病的蛋白，它的突變會導(dǎo)致智力殘疾,。雖然所有的細(xì)胞在其表面上存在一個受體數(shù)量監(jiān)管系統(tǒng),，但在阿爾茨海默氏癥中，受體往往會加速消逝,，如此神經(jīng)元與神經(jīng)元的溝通也減少,。
研究發(fā)現(xiàn)神經(jīng)遞質(zhì)谷氨酸有助于建立和維護(hù)突觸，并有助于GluN2B與突觸結(jié)合,。事實(shí)上,，這些受體的數(shù)目隨著年齡的增長而降低，這可能是青少年學(xué)習(xí)起來更容易的原因之一,。（生物谷：Bioon.com）
doi:10.1016/j.celrep.2012.09.024
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SAP102 Mediates Synaptic Clearance of NMDA Receptors
Bo-Shiun Chen, John A. Gray, Antonio Sanz-Clemente, Zhe Wei, Eleanor V. Thomas, Roger A. Nicoll, Katherine W. Roche.
Membrane-associated guanylate kinases (MAGUKs) are the major family of scaffolding proteins at the postsynaptic density. The PSD-MAGUK subfamily, which includes PSD-95, PSD-93, SAP97, and SAP102, is well accepted to be primarily involved in the synaptic anchoring of numerous proteins, including N-methyl-D-aspartate receptors (NMDARs). Notably, the synaptic targeting of NMDARs depends on the binding of the PDZ ligand on the GluN2B subunit to MAGUK PDZ domains, as disruption of this interaction dramatically decreases NMDAR surface and synaptic expression. We recently reported a secondary interaction between SAP102 and GluN2B, in addition to the PDZ interaction. Here, we identify two critical residues on GluN2B responsible for the non-PDZ binding to SAP102. Strikingly, either mutation of these critical residues or knockdown of endogenous SAP102 can rescue the defective surface expression and synaptic localization of PDZ binding-deficient GluN2B. These data reveal an unexpected, nonscaffolding role for SAP102 in the synaptic clearance of GluN2B-containing NMDARs.
