Fragile X mental retardation protein interacts with the RNA-binding protein Caprin1 in neuronal RiboNucleoProtein complexes [corrected].
Fragile X mental retardation protein interacts with the RNA-binding protein Caprin1 in neuronal RiboNucleoProtein complexes [corrected].
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DOI：
10.1371/journal.pone.0039338
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Khandjian EW
中科院分区：
文献类型：
--
作者：
El Fatimy R;Tremblay S;Dury AY;Solomon S;De Koninck P;Schrader JW;Khandjian EW
脆性X综合征是由于缺乏脆性X智力低下蛋白(FMRP)引起的，FMRP是一种RNA结合蛋白。FMRP与多聚核糖体中存在的信使核核蛋白(MRNPs)相关，它在神经元中的缺失导致翻译调节缺陷导致突触可塑性的改变。FMRP在翻译调控中发挥作用的分子机制仍然不清楚。利用单抗Ab7G1-1和新一代鸡抗体的免疫沉淀方法，我们鉴定了CAPRIN1是一个新的FMRP-细胞伙伴。体内和体外证据表明，CAPRIN1与FMRP在翻译机制和运输神经元颗粒的水平上相互作用。作为一种RNA结合蛋白，CAPRIN1与FMRP至少有两个RNA靶点，分别是CaMKIIα和Map1b mRNAs。鉴于FMRP物种与RNA结合的新概念，无论已知的结构基序如何，我们认为蛋白质相互作用可能调节FMRP的功能。
Fragile X syndrome is caused by the absence of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein. FMRP is associated with messenger RiboNucleoParticles (mRNPs) present in polyribosomes and its absence in neurons leads to alteration in synaptic plasticity as a result of translation regulation defects. The molecular mechanisms by which FMRP plays a role in translation regulation remain elusive. Using immunoprecipitation approaches with monoclonal Ab7G1-1 and a new generation of chicken antibodies, we identified Caprin1 as a novel FMRP-cellular partner. In vivo and in vitro evidence show that Caprin1 interacts with FMRP at the level of the translation machinery as well as in trafficking neuronal granules. As an RNA-binding protein, Caprin1 has in common with FMRP at least two RNA targets that have been identified as CaMKIIα and Map1b mRNAs. In view of the new concept that FMRP species bind to RNA regardless of known structural motifs, we propose that protein interactors might modulate FMRP functions.