| First Author | Wang Q | Year | 2010 |
| Journal | Circ Res | Volume | 106 |
| Issue | 9 | Pages | 1468-78 |
| PubMed ID | 20360251 | Mgi Jnum | J:158491 |
| Mgi Id | MGI:4438861 | Doi | 10.1161/CIRCRESAHA.109.212787 |
| Citation | Wang Q, et al. (2010) Essential roles of an intercalated disc protein, mXinbeta, in postnatal heart growth and survival. Circ Res 106(9):1468-78 |
| abstractText | RATIONALE: The Xin repeat-containing proteins mXinalpha and mXinbeta localize to the intercalated disc of mouse heart and are implicated in cardiac development and function. The mXinalpha directly interacts with beta-catenin, p120-catenin, and actin filaments. Ablation of mXinalpha results in adult late-onset cardiomyopathy with conduction defects. An upregulation of the mXinbeta in mXinalpha-deficient hearts suggests a partial compensation. OBJECTIVE: The essential roles of mXinbeta in cardiac development and intercalated disc maturation were investigated. METHODS AND RESULTS: Ablation of mXinbeta led to abnormal heart shape, ventricular septal defects, severe growth retardation, and postnatal lethality with no upregulation of the mXinalpha. Postnatal upregulation of mXinbeta in wild-type hearts, as well as altered apoptosis and proliferation in mXinbeta-null hearts, suggests that mXinbeta is required for postnatal heart remodeling. The mXinbeta-null hearts exhibited a misorganized myocardium as detected by histological and electron microscopic studies and an impaired diastolic function, as suggested by echocardiography and a delay in switching off the slow skeletal troponin I. Loss of mXinbeta resulted in the failure of forming mature intercalated discs and the mislocalization of mXinalpha and N-cadherin. The mXinbeta-null hearts showed upregulation of active Stat3 (signal transducer and activator of transcription 3) and downregulation of the activities of Rac1, insulin-like growth factor 1 receptor, protein kinase B, and extracellular signal-regulated kinases 1 and 2. CONCLUSIONS: These findings identify not only an essential role of mXinbeta in the intercalated disc maturation but also mechanisms of mXinbeta modulating N-cadherin-mediated adhesion signaling and its crosstalk signaling for postnatal heart growth and animal survival. |
