Proteomic analysis reveals CCT is a target of Fragile X mental retardation protein regulation in Drosophila.
Proteomic analysis reveals CCT is a target of Fragile X mental retardation protein regulation in Drosophila.
复制标题
蛋白质组学分析表明，CCT 是果蝇脆性 X 智力迟钝蛋白调节的目标。
DOI：
10.1016/j.ydbio.2010.01.028
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发表时间：
2010
影响因子：
2.7
通讯作者：
Sisson,JohnC
中科院分区：
文献类型：
--
作者：
Monzo,Kate;Dowd,SusanR;Minden,JonathanS;Sisson,JohnC
脆性X智力低下蛋白(FMRP)是一种RNA结合蛋白，对特定的靶mRNAs的翻译调控是必需的。FMRP的缺失会导致脆性X综合征(FXS)，这是人类最常见的遗传性智力低下形式。对FXS的基础了解有限，因为FMRP的体内靶点很少，FMRP如何调节生理靶点的机制也不清楚。我们先前已经证明，果蝇FMRP(DFMRP)在早期胚胎中是形成卵裂沟所必需的。为了找出dFMRP依赖调控的新靶点和卵裂沟形成的新效应因子，我们使用双向差示凝胶电泳和质谱仪来鉴定在dfmr1突变胚胎中错误表达的蛋白质。在已鉴定的28种蛋白质中，我们已经确定含有TCP-1(CCT)复合体的伴侣蛋白的三个亚基是dFMRP依赖调控的新的直接靶点。此外，我们还发现已知的卵裂效应因子Septin花生可能是Fly CCT的保守底物，并且在CCT和dfmr1突变胚胎中都错误定位。基于这些结果，我们认为，在dfmr1−胚胎中，依赖于dFMRP的Cct亚基的调节是卵裂沟形成所必需的，并且至少有一个底物受到影响，这表明依赖dFMRP的Cct调节有助于卵裂沟的形成。
Fragile X mental retardation protein (FMRP) is an RNA-binding protein that is required for the translational regulation of specific target mRNAs. Loss of FMRP causes Fragile X syndrome (FXS), the most common form of inherited mental retardation in humans. Understanding the basis for FXS has been limited because few in vivo targets of FMRP have been identified and mechanisms for how FMRP regulates physiological targets are unclear. We have previously demonstrated that Drosophila FMRP (dFMRP) is required in early embryos for cleavage furrow formation. In an effort to identify new targets of dFMRP-dependent regulation and new effectors of cleavage furrow formation, we used two-dimensional difference gel electrophoresis and mass spectrometry to identify proteins that are misexpressed in dfmr1 mutant embryos. Of the 28 proteins identified, we have identified three subunits of the Chaperonin containing TCP-1 (CCT) complex as new direct targets of dFMRP-dependent regulation. Furthermore, we found that the septin Peanut, a known effector of cleavage, is a likely conserved substrate of fly CCT and is mislocalized in both cct and in dfmr1 mutant embryos. Based on these results we propose that dFMRP-dependent regulation of CCT subunits is required for cleavage furrow formation and that at least one of its substrates is affected in dfmr1− embryos suggesting that dFMRP-dependent regulation of CCT contributes to the cleavage furrow formation phenotype.