Structural compartments within neurons: Developmentally regulated organization of microfilament isoform mRNA and protein

Structural compartments within neurons: Developmentally regulated organization of microfilament isoform mRNA and protein
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DOI:
10.1006/mcne.1998.0693
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发表时间:
1998-08-01
影响因子:
3.5
通讯作者:
Weinberger, RP
Weinberger, RP
中科院分区:
医学3区
文献类型:
--
作者:
Hannan, AJ;Gunning, P;Weinberger, RP

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微丝系统被认为是调节神经元发育和成熟功能的重要细胞骨架成分。细胞内分布的微丝异构体组件,肌动蛋白和原肌球蛋白(Tm),主要在体内的神经元,已在mRNA和蛋白质水平上使用异构体特异性核糖核酸探针和抗体进行了研究。我们在体内和体外的研究已经确定了至少六个神经元隔室的基础上微丝异构体mRNA的定位:发育中的索马,成熟的索马,生长锥,发育中的轴突丘/近端轴突,成熟的体树突和成熟的轴突极索马。蛋白质定位模式显示,异构体经常分布在一个更广泛的区域比各自的mRNA,这表明异构体的mRNA靶向的特定模式可能会影响,但不能绝对确定,微丝异构体的位置。Tm 4和Tm 5在发育神经元中显示相同的mRNA靶向,但不同的蛋白定位模式。我们认为,在这种情况下,mRNA的位置可能最好被视为一个受管制的网站的合成和组装,而不是调节蛋白质定位本身。此外,Tm 5和p-actin的mRNA和蛋白质的位置发育调节,这表明环境信号调节特定的mRNA及其蛋白质的靶向的可能性。因此,发育调节的mRNA定位和位置翻译可能与蛋白质转运协同作用,以调节神经元微丝组成,从而调节神经元结构。
The microfilament system is thought to be a crucial cytoskeletal component regulating development and mature function of neurons. The intracellular distribution of the microfilament isoform components, actin and tropomyosin (Tm), in neurons primarily in vivo, has been investigated at both the mRNA and the protein level using isoform specific riboprobes and antibodies. Our in vivo and in vitro studies have identified at least six neuronal compartments based on microfilament isoform mRNA localization: the developing soma, the mature soma, growth cone, developing axon hillock/proximal axon, Mature somatodendritic and mature axonal pole soma. Protein localization patterns revealed that the isoforms were frequently distributed over a wider area than their respective mRNAs, suggesting that isoform specific patterns of mRNA targeting may influence, but do not absolutely determine, microfilament isoform location. Tm4 and Tm5 showed identical mRNA targeting in the developing neuron but distinct protein localization patterns. We suggest that in this instance mRNA location may best be viewed as a regulated site of synthesis and assembly, rather than a regulator of protein localization per se. In addition, Tm5 and p-actin mRNA and protein locations were developmentally regulated, suggesting the possibility that environmental signals modulate targeting of specific mRNAs and their proteins. Thus, developmentally regulated mRNA localization and positional translation may act in concert with protein transport to regulate neuronal microfilament composition and consequently neuronal structure.