科學(xué)家對(duì)大腦中一種叫朊病毒的正常蛋白可以變得有害并導(dǎo)致人類克雅病和牛綿狀腦?。ǒ偱２,。┑恼J(rèn)識(shí)已經(jīng)20多年了,，但至今仍然不能解釋，我們?nèi)梭w中早先為什么會(huì)產(chǎn)生大量的這種蛋白,。德國(guó)康斯坦茨大學(xué)研究人員最近發(fā)現(xiàn),，朊病毒蛋白實(shí)際起了一個(gè)對(duì)生物體有益的作用，它能在胚胎發(fā)育期間幫助細(xì)胞之間進(jìn)行交流,。
發(fā)生朊病毒疾病的原因是它的化學(xué)結(jié)構(gòu)發(fā)生了改變,，使正常的朊病毒蛋白轉(zhuǎn)變?yōu)閷?duì)生命有威脅的物質(zhì)。此外,，朊病毒還具有將異常結(jié)構(gòu)傳給健康朊病毒蛋白的復(fù)制能力,，因此會(huì)產(chǎn)生新的致病體。盡管這種變化過程可以解釋朊病毒是如何播散的,，但朊病毒蛋白的異常功能是神經(jīng)退行性疾病發(fā)生的根源,。多年來，對(duì)朊病毒正常功能的認(rèn)識(shí)一直是個(gè)不解之謎,。到目前為止,，所有對(duì)遺傳改良小鼠的研究都沒有提供確切的證據(jù)，因?yàn)檫@些小鼠缺乏完全健康的朊病毒蛋白,。
康斯坦茨大學(xué)最近證明，缺乏朊病毒蛋白可明顯造成動(dòng)物生理上的異常，而他們用的試驗(yàn)?zāi)Ｐ褪俏⑿〉陌唏R魚,。當(dāng)研究人員給斑馬魚胚胎注射少量抑制朊病毒蛋白產(chǎn)生的,、類似DNA分子樣的物質(zhì)嗎啉代后，這些斑馬魚的胚胎就不能正常發(fā)育,，最終導(dǎo)致了死亡,。正常見于斑馬魚胚胎中細(xì)胞與細(xì)胞結(jié)合部位的朊病毒蛋白消失，致使這些細(xì)胞不能進(jìn)行交流和進(jìn)行正常的,、形成身體主要結(jié)構(gòu)的分化程序,，包括神經(jīng)系統(tǒng)。
“我們證明,，朊病毒蛋白是一種膠合元素,，它將細(xì)胞聚合在一起并使它們保持聯(lián)絡(luò)。”研究人員說,。“當(dāng)兩個(gè)相鄰細(xì)胞進(jìn)行聯(lián)絡(luò)時(shí),，它們就能交換影響身體組織功能的重要信號(hào)。”
盡管這項(xiàng)研究沒有提供治療克-雅病和牛綿狀腦病的方法,，但揭開了部分復(fù)雜難題,，拓寬了我們對(duì)朊病毒疾病的認(rèn)識(shí)，也為有效治療這類疾病帶來了希望,。（生物谷Bioon.com）
生物谷推薦原始出處：
PLoS Biol 7(3): e1000055 doi:10.1371/journal.pbio.1000055
Regulation of Embryonic Cell Adhesion by the Prion Protein
Edward Málaga-Trillo*, Gonzalo P. Solis, Yvonne Schrock, Corinna Geiss, Lydia Luncz, Venus Thomanetz, Claudia A. O. Stuermer
Department of Biology, University of Konstanz, Konstanz, Germany
Prion proteins (PrPs) are key players in fatal neurodegenerative disorders, yet their physiological functions remain unclear, as PrP knockout mice develop rather normally. We report a strong PrP loss-of-function phenotype in zebrafish embryos, characterized by the loss of embryonic cell adhesion and arrested gastrulation. Zebrafish and mouse PrP mRNAs can partially rescue this knockdown phenotype, indicating conserved PrP functions. Using zebrafish, mouse, and Drosophila cells, we show that PrP: (1) mediates Ca+2-independent homophilic cell adhesion and signaling; and (2) modulates Ca+2-dependent cell adhesion by regulating the delivery of E-cadherin to the plasma membrane. In vivo time-lapse analyses reveal that the arrested gastrulation in PrP knockdown embryos is due to deficient morphogenetic cell movements, which rely on E-cadherin–based adhesion. Cell-transplantation experiments indicate that the regulation of embryonic cell adhesion by PrP is cell-autonomous. Moreover, we find that the local accumulation of PrP at cell contact sites is concomitant with the activation of Src-related kinases, the recruitment of reggie/flotillin microdomains, and the reorganization of the actin cytoskeleton, consistent with a role of PrP in the modulation of cell adhesion via signaling. Altogether, our data uncover evolutionarily conserved roles of PrP in cell communication, which ultimately impinge on the stability of adherens cell junctions during embryonic development.
