Characterization of nebulette and nebulin and emerging concepts of their roles for vertebrate Z-discs
Characterization of nebulette and nebulin and emerging concepts of their roles for vertebrate Z-discs
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DOI：
10.1006/jmbi.1998.1999
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发表时间：
1998-09-11
影响因子：
5.6
通讯作者：
Labeit, S
中科院分区：
文献类型：
--
作者：
Millevoi, S;Trombitas, K;Labeit, S
Nebulin 是一种 800 kDa 的大型肌动蛋白结合蛋白，对骨骼肌具有特异性，被认为可作为调节细丝长度的分子模板。最近，在禽类心肌中发现了一种 100 kDa 的星云蛋白样蛋白，被称为星云蛋白。我们已经确定了人类星云的全长 (8 kb) cDNA 序列。其开放阅读框（3044 bp）编码一个 109 kDa 的蛋白质，与人星云蛋白的 C 末端区域具有广泛的相似性。 nebulin 和 nebulette 的 C 端区域在结构域组织上是相同的，并且共享一系列高度相关的 C 端重复序列、具有潜在磷酸化位点的富含丝氨酸的结构域以及 SH3 结构域。免疫电子显微镜表明，星云蛋白和星云丝的 C 端 30 kDa 整合到 Z 盘晶格中，而它们的 N 端似乎投射到 I 带中。基因图谱研究将人类 nebulette 基因分配至染色体 10p12，而 nebulin 基因此前已分配至 2q21。进化限制似乎在这两个独立基因中保持了相同的模块排列。星云蛋白和星云 cDNA 的比较表明，C 末端区域内的重复亚组在两种分子的发育过程中受到组织特异性和阶段依赖性的调节。这导致星云蛋白和星云亚型的显着多样性。他们的进一步研究可能会深入了解它们如何促进不同肌肉组织和纤维类型的 Z 盘分子多样性。 (C) 1998 年学术出版社。
Nebulin is an 800 kDa large actin-binding protein specific to skeletal muscle and thought to act as a molecular template that regulates the length of thin filaments. Recently, a 100 kDa nebulin-like protein has been described in the avian cardiac muscle and referred to as nebulette. We have determined the full-length (8 kb) cDNA sequence of the human nebulette. Its open reading frame (3044 bp) encodes a 109 kDa protein that shares extensive similarity with the C-terminal region of human nebulin. The C-terminal regions of nebulin and nebulette are identical in domain organization and share a family of highly related C-terminal repeats, a serine-rich domain with potential phosphorylation sites, and an SH3 domain. Immunoelectron-microscopy suggests that the C-terminal 30 kDa of nebulin and nebulette filaments integrate into the Z-disc lattice, whereas their N termini appear to project into the I-band. Gene mapping studies assign the human nebulette gene to chromosome 10p12, whereas the nebulin gene has been previously assigned to 2q21. Evolutionary constraints appear to have maintained identical modular arrangements in these two independent genes. Comparison of nebulin and nebulette cDNAs demonstrates that a subgroup of repeats within the C-terminal regions is regulated tissue-specifically and stage-dependently during development of both molecules. This leads to a substantial diversity of,nebulin and nebulette isoforms. Their further study is Likely to provide insights into how they contribute to the molecular diversity of Z-discs from different muscle tissues and fiber types. (C) 1998 Academic Press.