The RNA binding protein fragile X mental retardation protein promotes myelin sheath growth.
The RNA binding protein fragile X mental retardation protein promotes myelin sheath growth.
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作者：
Doll CA;Yergert KM;Appel BH
在发育过程中，中枢神经系统中的少突胶质细胞延伸出许多用髓鞘包裹轴突的突起。高度极化的少突胶质细胞在许多不同的轴突上产生髓鞘，这些轴突远离细胞体。神经元使用RNA结合蛋白来运输、稳定和局部翻译神经元远端结构域中的mRNA。在神经发育过程中，突触蛋白的局部合成促进了神经可塑性的快速结构和功能变化，并避免了广泛的蛋白质运输。我们假设RNA结合蛋白也调节少突胶质细胞中的局部mRNA调节以促进髓鞘生长。脆性X智力低下蛋白（FMRP）是一种RNA结合蛋白，在神经元的生长和成熟中起重要作用，也在少突胶质细胞中表达。为了确定少突胶质细胞是否需要FMRP来进行髓鞘发育，我们检测了fmr 1 −/−突变的斑马鱼，并特异性地在少突胶质细胞中驱动FMR 1表达。我们发现fmr 1 −/−突变体中的少突胶质细胞产生了长度减少的髓鞘，这是一种可以在FMR 1表达的少突胶质细胞中自主拯救的表型。髓鞘碱性蛋白（Mbp）是一种必需的髓鞘蛋白，在fmr 1 −/−突变体的髓鞘束中减少，但FMRP功能的丧失并不影响mbpa转录物在髓鞘中的定位。最后，FMR 1-I304 N（一种消除FMRP与核糖体关联的错义等位基因）的表达未能挽救fmr 1 −/−突变体鞘的生长，并诱导野生型幼虫少突胶质细胞中的短髓鞘。总之，这些数据表明，FMRP促进鞘生长通过本地调节翻译。
During development, oligodendrocytes in the central nervous system extend a multitude of processes that wrap axons with myelin. The highly polarized oligodendrocytes generate myelin sheaths on many different axons, which are far removed from the cell body. Neurons use RNA binding proteins to transport, stabilize, and locally translate mRNA in distal domains of neurons. Local synthesis of synaptic proteins during neurodevelopment facilitates the rapid structural and functional changes underlying neural plasticity and avoids extensive protein transport. We hypothesize that RNA binding proteins also regulate local mRNA regulation in oligodendrocytes to promote myelin sheath growth. Fragile X mental retardation protein (FMRP), an RNA binding protein that plays essential roles in the growth and maturation of neurons, is also expressed in oligodendrocytes. To determine whether oligodendrocytes require FMRP for myelin sheath development, we examined fmr1−/− mutant zebrafish and drove FMR1 expression specifically in oligodendrocytes. We found oligodendrocytes in fmr1−/− mutants developed myelin sheaths of diminished length, a phenotype that can be autonomously rescued in oligodendrocytes with FMR1 expression. Myelin basic protein (Mbp), an essential myelin protein, was reduced in myelin tracts of fmr1−/− mutants, but loss of FMRP function did not impact the localization of mbpa transcript in myelin. Finally, expression of FMR1-I304N, a missense allele that abrogates FMRP association with ribosomes, failed to rescue fmr1−/− mutant sheath growth and induced short myelin sheaths in oligodendrocytes of wild-type larvae. Taken together, these data suggest that FMRP promotes sheath growth through local regulation of translation.
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DOI：
10.1073/pnas.1010564107
发表时间：
2010-08-31
影响因子：
11.1
作者：
Kao, Der-I;Aldridge, Georgina M.;Greenough, William T.
通讯作者：
Greenough, William T.
影响因子：
4.5
作者：
Hornig J;Fröb F;Vogl MR;Hermans-Borgmeyer I;Tamm ER;Wegner M
通讯作者：
Wegner M
影响因子：
3.5
作者：
Giampetruzzi, Anthony;Carson, John H.;Barbarese, Elisa
通讯作者：
Barbarese, Elisa
影响因子：
56.9
作者：
Femino, A;Fay, FS;Singer, RH
通讯作者：
Singer, RH
神经元活动会影响体内髓鞘形成的轴突选择。
影响因子：
25
作者：
Hines, Jacob H.;Ravanelli, Andrew M.;Schwindt, Rani;Scott, Ethan K.;Appel, Bruce
通讯作者：
Appel, Bruce