ApoE receptor 2 regulates synapse and dendritic spine formation.

ApoE receptor 2 regulates synapse and dendritic spine formation.
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DOI:
10.1371/journal.pone.0017203
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发表时间:
2011-02-15
期刊:
影响因子:
3.7
通讯作者:
Hoe HS
Hoe HS
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dumanis SB;Cha HJ;Song JM;Trotter JH;Spitzer M;Lee JY;Weeber EJ;Turner RS;Pak DT;Rebeck GW;Hoe HS

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载脂蛋白E受体2(ApoEr 2)是一种突触后蛋白,通过未知机制参与长时程增强(LTP)、学习和记忆。我们研究了ApoEr 2对突触和树突棘形成过程的生物学效应,这些过程对学习和记忆至关重要。在异源共培养突触测定中,在COS 7细胞中ApoEr 2的过表达显著增加了与原代海马神经元中突触素的共定位,表明ApoEr 2促进与突触前结构的相互作用。在原代神经元培养中,ApoEr 2的过表达增加了树突棘密度。与我们的体外研究结果一致,ApoEr 2敲除小鼠在1月龄时皮质层II/III中的树突棘密度降低。我们还测试了ApoEr 2与其胞质衔接蛋白(特别是X11α和PSD-95)之间的相互作用是否影响突触和树突棘的形成。X11α沿着降低细胞表面ApoEr 2水平以及突触和树突棘密度。相比之下,PSD-95增加ApoEr 2的细胞表面水平以及突触和树突棘密度。这些结果表明ApoEr 2在中枢神经系统突触和树突棘的结构和功能中起着重要作用,并且这些作用受到胞质衔接蛋白X11α和PSD-95的调节。
Apolipoprotein E receptor 2 (ApoEr2) is a postsynaptic protein involved in long-term potentiation (LTP), learning, and memory through unknown mechanisms. We examined the biological effects of ApoEr2 on synapse and dendritic spine formation—processes critical for learning and memory. In a heterologous co-culture synapse assay, overexpression of ApoEr2 in COS7 cells significantly increased colocalization with synaptophysin in primary hippocampal neurons, suggesting that ApoEr2 promotes interaction with presynaptic structures. In primary neuronal cultures, overexpression of ApoEr2 increased dendritic spine density. Consistent with our in vitro findings, ApoEr2 knockout mice had decreased dendritic spine density in cortical layers II/III at 1 month of age. We also tested whether the interaction between ApoEr2 and its cytoplasmic adaptor proteins, specifically X11α and PSD-95, affected synapse and dendritic spine formation. X11α decreased cell surface levels of ApoEr2 along with synapse and dendritic spine density. In contrast, PSD-95 increased cell surface levels of ApoEr2 as well as synapse and dendritic spine density. These results suggest that ApoEr2 plays important roles in structure and function of CNS synapses and dendritic spines, and that these roles are modulated by cytoplasmic adaptor proteins X11α and PSD-95.
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