| First Author | Jung-Ching Lin J | Year | 2005 |
| Journal | J Med Sci | Volume | 25 |
| Issue | 5 | Pages | 215-222 |
| PubMed ID | 16708114 | Mgi Jnum | J:112201 |
| Mgi Id | MGI:3655786 | Doi | 10.1901/jaba.2005.25-215 |
| Citation | Jung-Ching Lin J, et al. (2005) Structure, Expression, and Function of a Novel Intercalated Disc Protein, Xin. J Med Sci 25(5):215-222 |
| abstractText | 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, mXinalpha and mXinbeta were identified and cloned. The human homologue of mXinalpha (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 mXinbeta (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 mXinalpha in Nkx2.5 or MEF2C knockout mouse embryos was drastically reduced, suggesting that mXinalpha 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 beta-catenin throughout mouse embryogenesis and into adulthood. Furthermore, mXinalpha appears to interact directly with beta-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/beta-catenin-and N-cadherin-mediated signaling pathways required for cardiac development and cardiac function. |
