加拿大麥吉爾大學(xué)生化系和古德曼癌癥研究所的科學(xué)家新近發(fā)現(xiàn)，哺乳動(dòng)物大腦使用一種特殊的方式對(duì)一種特別的蛋白質(zhì)4E-BP2進(jìn)行修改,，從而導(dǎo)致了蛋白質(zhì)正常功能的改變。目前,，大腦蛋白質(zhì)合成研究和記憶研究日益受到重視。專(zhuān)家認(rèn)為,，此次研究成果屬于該領(lǐng)域取得的重要成就,，在了解人類(lèi)大腦的工作機(jī)理研究上前進(jìn)了重要的一步。相關(guān)文章發(fā)表在3月25日出版的《分子細(xì)胞》雜志上,。
當(dāng)我們的記憶形成時(shí),，神經(jīng)細(xì)胞或神經(jīng)元之間使用專(zhuān)門(mén)的聯(lián)接通過(guò)電脈沖進(jìn)行相互交流。為了加強(qiáng)這些專(zhuān)門(mén)的聯(lián)接,，神經(jīng)元就需要新的蛋白質(zhì),，這些新蛋白質(zhì)即是用于各種形式的蜂窩活動(dòng)所需的關(guān)鍵分子。
這種特別的蛋白質(zhì)的代號(hào)為4E-BP2,，在神經(jīng)系統(tǒng)中它控制了產(chǎn)生新蛋白質(zhì)的整個(gè)過(guò)程,，即蛋白質(zhì)的合成或轉(zhuǎn)移，這是研究人員的主要研究焦點(diǎn),。在此之前,，還沒(méi)有任何人知道可將4E-BP2蛋白質(zhì)通過(guò)化學(xué)方法進(jìn)行修改。據(jù)研究小組負(fù)責(zé)人比蒂諾斯蒂博士介紹,，他們所發(fā)現(xiàn)的蛋白質(zhì)修改,，控制了蜂窩蛋白質(zhì)合成的形式。這種修改還似乎影響了神經(jīng)元之間的相互溝通能力,。同時(shí),，這種修改也是影響記憶過(guò)程的一個(gè)因素。
加拿大衛(wèi)生研究所科研主管菲利普斯博士認(rèn)為,，更好地了解大腦中蛋白質(zhì)的合成,，對(duì)神經(jīng)學(xué)研究工作非常重要；特別是該項(xiàng)新發(fā)現(xiàn)表明，修改的蛋白質(zhì)可能對(duì)記憶過(guò)程有直接的影響,，該項(xiàng)成果對(duì)最終攻克治療記憶喪失等問(wèn)題有重要價(jià)值。(生物谷Bioon.com)
生物谷推薦原文出處：
Molecular Cell 10.1016/j.molcel.2010.02.022
Postnatal Deamidation of 4E-BP2 in Brain Enhances Its Association with Raptor and Alters Kinetics of Excitatory Synaptic Transmission
Michael Bidinosti, Israeli Ran, Maria R. Sanchez-Carbente, Yvan Martineau, Anne-Claude Gingras, Christos Gkogkas, Brian Raught, Clive R. Bramham, Wayne S. Sossin, Mauro Costa-Mattioli, Luc DesGroseillers, Jean-Claude Lacaille, Nahum Sonenberg
The eIF4E-binding proteins (4E-BPs) repress translation initiation by preventing eIF4F complex formation. Of the three mammalian 4E-BPs, only 4E-BP2 is enriched in the mammalian brain and plays an important role in synaptic plasticity and learning and memory formation. Here we describe asparagine deamidation as a brain-specific posttranslational modification of 4E-BP2. Deamidation is the spontaneous conversion of asparagines to aspartates. Two deamidation sites were mapped to an asparagine-rich sequence unique to 4E-BP2. Deamidated 4E-BP2 exhibits increased binding to the mammalian target of rapamycin (mTOR)-binding protein raptor, which effects its reduced association with eIF4E. 4E-BP2 deamidation occurs during postnatal development, concomitant with the attenuation of the activity of the PI3K-Akt-mTOR signaling pathway. Expression of deamidated 4E-BP2 in 4E-BP2?/? neurons yielded mEPSCs exhibiting increased charge transfer with slower rise and decay kinetics relative to the wild-type form. 4E-BP2 deamidation may represent a compensatory mechanism for the developmental reduction of PI3K-Akt-mTOR signaling.
