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A Fresh Look at the Structure, Regulation, and Functions of Fodrin.
Molecular and Cellular Biology ( IF 5.3 ) Pub Date : 2020-08-14 , DOI: 10.1128/mcb.00133-20
Jamuna S Sreeja 1 , Rince John 1 , Dhrishya Dharmapal 1 , Rohith Kumar Nellikka 1 , Suparna Sengupta 2
Affiliation  

Fodrin and its erythroid cell-specific isoform spectrin are actin-associated fibrous proteins that play crucial roles in the maintenance of structural integrity in mammalian cells, which is necessary for proper cell function. Normal cell morphology is altered in diseases such as various cancers and certain neuronal disorders. Fodrin and spectrin are two-chain (αβ) molecules that are encoded by paralogous genes and share many features but also demonstrate certain differences. Fodrin (in humans, typically a heterodimer of the products of the SPTAN1 and SPTBN1 genes) is expressed in nearly all cell types and is especially abundant in neuronal tissues, whereas spectrin (in humans, a heterodimer of the products of the SPTA1 and SPTB1 genes) is expressed almost exclusively in erythrocytes. To fulfill a role in such a variety of different cell types, it was anticipated that fodrin would need to be a more versatile scaffold than spectrin. Indeed, as summarized here, domains unique to fodrin and its regulation by Ca2+, calmodulin, and a variety of posttranslational modifications (PTMs) endow fodrin with additional specific functions. However, how fodrin structural variations and misregulated PTMs may contribute to the etiology of various cancers and neurodegenerative diseases needs to be further investigated.

中文翻译:

重新审视Fodrin的结构,调控和功能。

Fodrin及其类红细胞特异性亚型血影蛋白是肌动蛋白相关的纤维蛋白,在维持哺乳动物细胞的结构完整性中起着至关重要的作用,这对于正常的细胞功能是必需的。在诸如各种癌症和某些神经元疾病之类的疾病中,正常细胞形态发生了改变。Fodrin和Spectrin是由旁系同源基因编码的双链(αβ)分子,具有许多特征,但也显示出一定的差异。Fodrin(在人类中,通常是SPTAN1和SPTBN1基因产物的异二聚体)在几乎所有细胞类型中表达,并且在神经元组织中尤其丰富,而血影蛋白(在人类中,SPTA1和SPTB1基因的产物是异二聚体) )几乎只在红细胞中表达。为了在各种不同的细胞类型中发挥作用,可以预料,与血影蛋白相比,铁蛋白将需要成为一种用途更广泛的支架。的确,正如此处总结的那样,铁蛋白的独特结构域及其受钙的调节2+,钙调蛋白和多种翻译后修饰(PTM)赋予了fodrin其他功能。但是,铁蛋白结构的变化和PTM​​的失控如何可能导致各种癌症和神经退行性疾病的病因学。
更新日期:2020-08-20
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