洛克菲勒大學(xué)的科學(xué)家已經(jīng)識別出一種叫Norbin的蛋白。該蛋白能夠增強(qiáng)大腦中某一參與大腦細(xì)胞信號傳遞的受體的信號強(qiáng)度,，或能成為精神分裂癥或帕金森氏癥新的治療靶標(biāo),。Norbin蛋白能直接作用于神經(jīng)遞質(zhì)素谷氨酸（glutamate）的一種受體，其中谷氨酸是腦細(xì)胞間傳遞信息所必需的,，其在學(xué)習(xí)和記憶過程中承擔(dān)了重要的作用。
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與Norbin關(guān)聯(lián)的一種受體是mGluR5,它是一種嵌入在細(xì)胞質(zhì)膜上,，能應(yīng)答配體小分子的蛋白質(zhì),。當(dāng)mGluR5綁定到配體時，會通過形狀改變產(chǎn)生應(yīng)答,，這最終導(dǎo)致細(xì)胞內(nèi)信號的初始化，其中我們最常見的就是G蛋白偶聯(lián)受體（GPCR）,。
"調(diào)控GPCR功能的蛋白質(zhì)和受體是同樣重要的,，因?yàn)樗且环N新的治療靶標(biāo)。"研究人員Marc Flajolet介紹說,。
研究人員發(fā)現(xiàn)了一些能與mGluR5進(jìn)行物理互作的蛋白，其中包括Norbin,。在培養(yǎng)的神經(jīng)元中,，他們將Norbin和mGluR5進(jìn)行配對，發(fā)現(xiàn)Norbin不僅僅激活了mGluR5的活性,，而且增加了神經(jīng)元表面mGluR5的數(shù)量。
在成年小鼠大腦中,，研究人員觀察了Norbin蛋白對mGluR5的影響,，結(jié)果表明，Norbin在海馬體,，扁桃腺,，隔膜和伏隔閡中的表現(xiàn)與那些mGluR5普遍分布的地方相似。
接下來研究人員通過遺傳學(xué)手段設(shè)計(jì)了一種選擇性敲除的老鼠,，該老鼠在出生后不能產(chǎn)生Norbin,。實(shí)驗(yàn)表明，這些老鼠缺乏突觸可塑性,，且行為表現(xiàn)與那些精神分裂的嚙齒動物模型相似,。比如,，Norbin敲除的老鼠會和正常老鼠一樣會被很大的噪聲所驚嚇,，但是如果隨后再置于噪聲環(huán)境下則不能抑制驚嚇反應(yīng),。
Flajolet表示,，"未來我們的工作是證明GPCR調(diào)控蛋白的重要性，我們現(xiàn)在正在研究Norbin影響mGluR5的機(jī)制,，并尋找能夠修飾Norbin功能的調(diào)控通路,。"(生物谷Bioon.net)
生物谷推薦原文出處：
Science DOI: 10.1126/science.1178496
Norbin Is an Endogenous Regulator of Metabotropic Glutamate Receptor 5 Signaling
Hong Wang,1 Linda Westin,2 Yi Nong,1 Shari Birnbaum,3 Jacob Bendor,1 Hjalmar Brismar,2,4 Eric Nestler,5 Anita Aperia,2 Marc Flajolet,1,* Paul Greengard1
Metabotropic glutamate receptor 5 (mGluR5) is highly expressed in the mammalian central nervous system (CNS). It is involved in multiple physiological functions and is a target for treatment of various CNS disorders, including schizophrenia. We report that Norbin, a neuron-specific protein, physically interacts with mGluR5 in vivo, increases the cell surface localization of the receptor, and positively regulates mGluR5 signaling. Genetic deletion of Norbin attenuates mGluR5-dependent stable changes in synaptic function measured as long-term depression or long-term potentiation of synaptic transmission in the hippocampus. As with mGluR5 knockout mice or mice treated with mGluR5-selective antagonists, Norbin knockout mice showed a behavioral phenotype associated with a rodent model of schizophrenia, as indexed by alterations both in sensorimotor gating and psychotomimetic-induced locomotor activity.
1 Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10065, USA.
2 Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital Q2:09, S-171 76 Stockholm, Sweden.
3 Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
4 Department of Applied Physics, Cell Physics, Royal Institute of Technology, S-106 91 Stockholm, Sweden.
5 Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.
