Muscle specific fragile X related protein 1 isoforms are sequestered in the nucleus of undifferentiated myoblast.
Muscle specific fragile X related protein 1 isoforms are sequestered in the nucleus of undifferentiated myoblast.
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DOI：
10.1186/1471-2156-1-4
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发表时间：
2000
期刊：
影响因子：
2.9
通讯作者：
Khandjian EW
中科院分区：
文献类型：
--
作者：
Dubé M;Huot ME;Khandjian EW
脆性X智力低下蛋白家族由三个成员组成：脆性智力低下1，脆性X相关1和X相关2蛋白。这些蛋白质与翻译核糖体内的mRNP相关，并具有在细胞核和细胞质之间穿梭的能力。FMRP因其在人类遗传性智力低下中的意义而受到极大关注，而FXR 1 P和FXR 2 P只是最近才被研究。使用针对FXR 1 P的几个表位的抗体，我们已经检测到由小肽口袋插入物产生的蛋白质同种型。分子量为70、74、78、80 kDa的四种异构体广泛分布于小鼠器官中，而在横纹肌中，这些异构体被含有27个氨基酸的额外口袋的82和84 kDa的蛋白质所取代。这些肌肉亚型的表达是成肌细胞体外分化为肌管的早期事件，并与肌肉特异性基因的激活相关。然而，虽然FXR 1 P82，84与肌管中的细胞质mRNP相关，但它们被隔离在未分化的成肌细胞的细胞核中。这些观察结果表明，除了尚未定义的细胞质功能外，FXR 1 P82，84可能在前mRNA代谢中发挥核作用。在FXR蛋白家族中，肌生成过程中FXR 1 P亚型的亚细胞分配模式是独特的。由于FXR 1 P作为脆性X综合征代偿因子的潜在作用仍然难以捉摸，因此本文描述的模型系统应被视为正在进行的试图解开不同FMR家族成员的结构-功能关系的有力工具。
The family of Fragile X Mental Retardation Proteins is composed of three members: Fragile Mental Retardation 1, Fragile X Related 1 and X Related 2 proteins. These proteins are associated with mRNPs within translating ribosomes and have the capacity to shuttle between the nucleus and the cytoplasm. Great attention has been given to FMRP due to its implication in human hereditary mental retardation while FXR1P and FXR2P have only recently been studied. Using antibodies directed against several epitopes of FXR1P, we have detected protein isoforms generated by small peptides pocket inserts. Four isoforms of MW 70, 74, 78, 80 kDa are widely distributed in mouse organs, while in striated muscles these isoforms are replaced by proteins of 82 and 84 kDa containing an extra pocket of 27 aa. Expression of these muscle isoforms is an early event during in vitro differentiation of myoblasts into myotubes and correlates with the activation of muscle-specific genes. However, while FXR1P82,84 are associated with cytoplasmic mRNPs in myotubes, they are sequestered in the nuclei of undifferentiated myoblasts. These observations suggest that, in addition to a cytoplasmic function yet to be defined, FXR1P82,84 may play a nuclear role in pre-mRNA metabolism. The pattern of subcellular partitioning of FXR1P isoforms during myogenesis is unique among the family of the FXR proteins. The model system described here should be considered as a powerful tool for ongoing attempts to unravel structure-function relationships of the different FMR family members since the potential role(s) of FXR1P as a compensatory factor in Fragile X syndrome is still elusive.