Drosophila Tubulin-specific chaperone E functions at neuromuscular synapses and is required for microtubule network formation
Drosophila Tubulin-specific chaperone E functions at neuromuscular synapses and is required for microtubule network formation
复制标题
果蝇微管蛋白特异性伴侣 E 在神经肌肉突触发挥作用，是微管网络形成所必需的
DOI：
10.1242/dev.029983
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发表时间：
2009-05-01
期刊：
影响因子：
4.6
通讯作者：
Zhang, Yong Q.
中科院分区：
文献类型：
--
作者：
Jin, Shan;Pan, Luyuan;Zhang, Yong Q.
甲状腺功能低下，智力低下和面部畸形（HRD）是由微管特异性伴侣E（TBCE）突变引起的致命发育疾病。小鼠TBCE突变会导致进行性运动神经疾病。为了剖析TBCE的功能和HRD的发病机理，我们在果蝇中产生了突变，并以组织特异性方式操纵其表达。果蝇TBCE无效是胚胎致死的。神经肌肉中TBCE的组织特异性敲低和过表达分别导致微管的破坏和增加。 TBCE表达的改变还会影响神经肌肉突触。遗传分析揭示了TBCE与微管蛋白痉挛之间的拮抗相互作用。此外，用微管 - 分解药物诺辅唑处理肌肉将TBCE视为微管蛋白聚合蛋白。综上所述，我们的结果表明，TBCE是神经肌肉突触的正常发育和功能所必需的，并且它促进了微管的形成。由于有缺陷的微管与许多神经系统和发育性疾病有关，因此我们在TBCE上的工作可能会为其基础提供新颖的见解。
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.