據(jù)中國(guó)科學(xué)院遺傳與發(fā)育生物學(xué)研究所最新消息,，該所發(fā)育生物學(xué)研究中心副主任張永清研究員領(lǐng)銜的研究小組在最新一期的Development上發(fā)表研究成果，文章標(biāo)題為：Drosophila Tubulin-specific chaperone E functions at neuromuscular synapses and is required for microtubule network formation,，主要解析了神經(jīng)肌肉突觸中微管蛋白特異伴侶蛋白E在微管網(wǎng)絡(luò)結(jié)構(gòu)發(fā)育過(guò)程中的重要作用,。
微管蛋白特異伴侶蛋白E（Tubulin-specific chaperone E，TBCE）,TBCE 是一種分布在細(xì)胞骨架,，微管中的蛋白,，主要與未折疊蛋白和伴侶蛋白結(jié)合，促進(jìn)蛋白折疊和β微管蛋白折疊,，如果發(fā)生異常會(huì)導(dǎo)致甲狀腺不足低下,，形態(tài)異常綜合征、Kenny-Caffey 綜合征(侏儒癥伴管狀骨皮質(zhì)增厚),，面部先天性畸形（Hypoparathyroidism, mental retardation and facial dysmorphism ,，HRD）等疾病的發(fā)生。
研究人員發(fā)現(xiàn),，如果小鼠的TBCE蛋白發(fā)生變異會(huì)導(dǎo)致運(yùn)動(dòng)神經(jīng)元發(fā)生退行性病變,。為了深入了解TBCE在HRD過(guò)程中所起的作用，張永清研究小組突變了生物模型果蠅的TBEC基因,，并可用特殊的技術(shù)控制TBCE基因在特定組織中的表達(dá)量,。
研究人員從完全缺失試驗(yàn)開(kāi)始，首先使得果蠅完全不表達(dá)TBCE蛋白,，結(jié)果導(dǎo)致果蠅胚胎無(wú)法正常發(fā)育最終死亡,。
研究人員又嘗試過(guò)度表達(dá)TBCE或是極低量表達(dá)TBCE蛋白,，結(jié)果果蠅都發(fā)生病變，過(guò)度表達(dá)導(dǎo)致微管大量形成,，過(guò)低表達(dá)導(dǎo)致微管功能紊亂,。并且研究還發(fā)現(xiàn)TBCE蛋白表達(dá)量發(fā)生變化還會(huì)影響神經(jīng)肌肉突觸的功能。
用遺傳分析手段研究發(fā)現(xiàn),，TBCE蛋白與植物微管切割蛋白Spastin（microtubule-severing protein Spastin）之間存在拮抗作用,，以上試驗(yàn)連同用微管解聚藥nocodazole處理肌肉的結(jié)果表明，TBCE蛋白是一種微管聚合蛋白（tubulin polymerizing protein）,。
這些研究結(jié)果表明TBCE蛋白在神經(jīng)肌肉突觸發(fā)育過(guò)程中起重要的作用,，尤其對(duì)微管的結(jié)構(gòu)的形成具有重要作用。這一結(jié)果為某些疾病的研究帶來(lái)了新的見(jiàn)解,。（生物谷Bioon.com）
生物谷推薦原始出處：
Development 18 Mar 2009 doi: 10.1242/dev.029983
Drosophila Tubulin-specific chaperone E functions at neuromuscular synapses and is required for microtubule network formation
Shan Jin, Luyuan Pan, Zhihua Liu, Qifu Wang, Zhiheng Xu, and Yong Q. Zhang*
Hypoparathyroidism, mental retardation and facial dysmorphism (HRD) is a fatal developmental disease caused by mutations in tubulin-specific chaperone E (TBCE). A mouse Tbce mutation causes progressive motor neuronopathy. To dissect the functions of TBCE and the pathogenesis of HRD, we generated mutations in Drosophila tbce, and manipulated its expression in a tissue-specific manner. Drosophila tbce nulls are embryonic lethal. Tissue-specific knockdown and overexpression of tbce in neuromusculature resulted in disrupted and increased microtubules, respectively. Alterations in TBCE expression also affected neuromuscular synapses. Genetic analyses revealed an antagonistic interaction between TBCE and the microtubule-severing protein Spastin. Moreover, treatment of muscles with the microtubule-depolymerizing drug nocodazole implicated TBCE as a tubulin polymerizing protein. Taken together, our results demonstrate that TBCE is required for the normal development and function of neuromuscular synapses and that it promotes microtubule formation. As defective microtubules are implicated in many neurological and developmental diseases, our work on TBCE may offer novel insights into their basis.
