St. Jude Children’s Research Hospital,、Loyoba大學(xué)和京都大學(xué)的研究人員發(fā)現(xiàn)用來調(diào)節(jié)新蛋白折疊的部分分子機(jī)制還包含一種遺傳性反應(yīng),這個反應(yīng)能夠擴(kuò)大蛋白質(zhì)折疊和包裝的工廠(內(nèi)質(zhì)網(wǎng)),。研究人員將這些發(fā)現(xiàn)公布在2004年10月15日的Journal of Cell Biology(JCB)上,。
蛋白質(zhì)折疊工廠(內(nèi)質(zhì)網(wǎng))的構(gòu)建之間的這種關(guān)連能夠確保這兩個過程在細(xì)胞需要快速制造,、折疊和分泌大量特定蛋白時能協(xié)調(diào)運(yùn)作。
研究人員發(fā)現(xiàn)細(xì)胞會產(chǎn)生一種叫做XBP1的分子以滿足蛋白質(zhì)折疊機(jī)器不斷增長的需要,。這種對折疊蛋白需求的增長會導(dǎo)致所謂的未折疊蛋白反應(yīng)(UPR)以及蛋白質(zhì)折疊和包裝的工廠的膨脹,。UPR還能促進(jìn)細(xì)胞產(chǎn)生分子伴侶,。
XBP1能夠引發(fā)細(xì)胞產(chǎn)生卵磷脂。卵磷脂是構(gòu)成內(nèi)質(zhì)網(wǎng)(ER)的重要建筑材料,。ER中的膜能充當(dāng)包裝已折疊蛋白的包膜,。當(dāng)離開ER后,這個包膜就會融合到細(xì)胞膜內(nèi)側(cè),。一旦融入細(xì)胞膜,,包膜就會打開并將其內(nèi)的蛋白質(zhì)放出細(xì)胞外。
通過將分子伴侶的制造和卵磷脂的合成聯(lián)系起來,,XBP1能夠協(xié)調(diào)新ER的構(gòu)建和裝備并以此提高細(xì)胞折疊和運(yùn)送蛋白的能力,。
研究人員通過對是小鼠的纖維原細(xì)胞的研究發(fā)現(xiàn)了這個機(jī)制。他們將XBP1基因插入一種病毒并利用這種轉(zhuǎn)基因病毒將這種基因引入纖維原細(xì)胞內(nèi),。XBP1基因使纖維原細(xì)胞膜產(chǎn)生有關(guān)的關(guān)鍵酶類的活性明顯增加,。因?yàn)椋呀?jīng)知道UPR能夠活化XBP1基因,,所以這項研究表明XBP1能夠?qū)R的膨脹和增加折疊和包裝分泌性蛋白的能力聯(lián)系在一起,。
這項研究解釋了細(xì)胞能夠快速滿足增加特定蛋白產(chǎn)量需求的原因,即通過折疊和裝配蛋白任務(wù)的協(xié)同來達(dá)成這種任務(wù),。而且,,這些發(fā)現(xiàn)也促進(jìn)了人們對細(xì)胞生物學(xué)的進(jìn)一步了解。
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