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Structural and functional diversity of novel coronin 1C (CRN2) isoforms in muscle.

机译:肌肉中新型冠状蛋白1C(CRN2)亚型的结构和功能多样性。

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摘要

Coronin 1C (synonyms: coronin-3, CRN2), a WD40 repeat-containing protein involved in cellular actin dynamics, is ubiquitously expressed in human tissues. Here, we report on the identification and functional characterization of two novel coronin 1C isoforms, referred to as CRN2i2 and CRN2i3, which also associate with F-actin. Analyses of the coronin 1C gene disclosed a single promoter containing binding sites for myogenic regulatory factors and an alternative first exon 1b present in intron 1, which give rise to the novel isoforms. Chromatin immunoprecipitation studies demonstrate MyoD binding to a region of the CRN2 gene, which contains a highly conserved E-box element in exon 1a. Gel-filtration assays suggest that the largest isoform 3 exists as a monomer, in contrast to isoform 1 and isoform 2 appearing as trimers. CRN2i3, which can be induced by MyoD, is exclusively expressed in well-differentiated myoblasts as well as in mature skeletal muscle tissue. In human skeletal muscle, CRN2i3 is a novel component of postsynaptic neuromuscular junctions and thin filaments of myofibrils. Together, our findings postulate a role for CRN2 isoforms in the structural and functional organization of F-actin in highly ordered protein complexes.
机译:Coronin 1C(同义词:coronin-3,CRN2)是一种参与细胞肌动蛋白动力学的WD40重复序列蛋白,在人体组织中普遍表达。在这里,我们报告两种新型冠状蛋白1C同工型,称为CRN2i2和CRN2i3,它们也与F-肌动蛋白相关的鉴定和功能表征。冠状蛋白1C基因的分析揭示了单个启动子,其包含肌调节因子的结合位点和内含子1中存在的替代性第一外显子1b,其产生了新的同工型。染色质免疫沉淀研究表明MyoD与CRN2基因区域结合,该区域在外显子1a中包含高度保守的E-box元件。凝胶过滤试验表明,最大的同工型3以单体形式存在,而同工型1和同工型2则表现为三聚体。可以由MyoD诱导的CRN2i3仅在分化良好的成肌细胞以及成熟的骨骼肌组织中表达。在人体骨骼肌中,CRN2i3是突触后神经肌肉接头和肌原纤维细丝的新型成分。在一起,我们的研究结果推测CRN2亚型在F-肌动蛋白的高度有序的蛋白质复合物的结构和功能组织中的作用。

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