Structure, Expression, and Function of a Novel Intercalated Disc Protein, Xin.
Structure, Expression, and Function of a Novel Intercalated Disc Protein, Xin.
复制标题
DOI：
10.1901/jaba.2005.25-215
复制
发表时间：
2005-10
期刊：
影响因子：
--
通讯作者：
Jim Jung-Ching Lin;Elisabeth A. Gustafson-Wagner;Haley W. Sinn;Sunju Choi;Shannon M Jaacks;Da-Zhi Wang;S. Evans;Jenny Li-Chun Lin
中科院分区：
文献类型：
--
作者：
Jim Jung-Ching Lin;Elisabeth A. Gustafson-Wagner;Haley W. Sinn;Sunju Choi;Shannon M Jaacks;Da-Zhi Wang;S. Evans;Jenny Li-Chun Lin
Xin 首次利用发育中鸡心脏的差异 mRNA 展示进行克隆。 Chick Xin (cXin) 参与 BMP-Nkx2.5-MEF2C 通路来调节心脏形态发生。通过随后的EST数据库检索和cDNA克隆，鉴定并克隆了两个小鼠Xin基因：mXinα和mXinβ。 mXinα 的人类同源物（名为 Cmya1）通过辐射杂交分析被定位到染色体 3p21.2-p21.3，最近通过 DNA 测序被定位到 3p22.2，该基因座靠近伴有传导缺陷 2 和致心律失常性右心室发育不良 5 的扩张型心肌病的基因座。通过 DNA 测序，预测的 mXinβ 人类同源物（名为 Cmya3）被定位到染色体 2q24.3。预测的 Xin 蛋白均包含一个新的 16 个氨基酸重复单元（Xin 重复单元）、一个推定的 DNA 结合域和核定位信号，以及一个富含脯氨酸的区域。来自小鸡和小鼠的所有三个 Xin 基因都具有相似的组织表达谱，仅限于横纹肌。 Nkx2.5 或 MEF2C 敲除小鼠胚胎中 mXinα 的表达显着降低，表明 mXinα 是 Nkx2.5 和 MEF2C 转录因子的下游靶标。另一方面，当小鼠承受压力超负荷引起的心脏肥大时，mXin 的表达上调。 Xin 蛋白在小鼠胚胎发生和成年期间与 N-钙粘蛋白和 β-连环蛋白共定位。此外，mXinα 似乎直接与 β-连环蛋白相互作用。 Xin 重复序列与肌动蛋白丝结合，也可能将微丝组织成网络。这些结果可能表明，Xin 通过整合粘附、组织插入位点的肌动蛋白丝排列以及调节心脏发育和心脏功能所需的 Wnt/β-连环蛋白和 N-钙粘蛋白介导的信号通路来发挥作用。
Xin was first cloned using differential mRNA display from the developing chicken heart. Chick Xin (cXin) participates in a BMP-Nkx2.5-MEF2C pathway to regulating cardiac morphogenesis. Through subsequent EST database searches and cDNA cloning, two mouse Xin genes, mXinα and mXinβ were identified and cloned. The human homologue of mXinα (named Cmya1) was mapped to chromosome 3p21.2-p21.3 by radiation hybrid analysis and recently to 3p22.2 by DNA sequencing, which is near the loci for a dilated cardiomyopathy with conduction defect-2 and arrhythmogenic right ventricular dysplasia-5. The predicted human homologue of mXinβ (named Cmya3) was mapped to chromosome 2q24.3 by DNA sequencing. Predicted Xin proteins all contain a novel 16-amino acid repeating unit (Xin repeat), a putative DNA binding domain and nuclear localization signal, as well as a proline-rich region. All three Xin genes from chick and mouse have a similar tissue expression profile, which is restricted to striated muscle. The expression of mXinα in Nkx2.5 or MEF2C knockout mouse embryos was drastically reduced, suggesting that mXinα is a downstream target of the Nkx2.5 and MEF2C transcription factors. On the other hand, the expression of mXin was up-regulated when mice were subjected to pressure overload-induced cardiac hypertrophy. Xin protein co-localizes with N-cadherin and β-catenin throughout mouse embryogenesis and into adulthood. Furthermore, mXinα appears to interact directly with β-catenin. The Xin repeats bind to actin filaments and may also organize microfilaments into networks. These results may suggest that Xin acts by integrating adhesion, by organizing actin filament arrangement at the insertion sites, and by regulating Wnt/β-catenin-and N-cadherin-mediated signaling pathways required for cardiac development and cardiac function.