| First Author | Wang Q | Year | 2013 |
| Journal | Dev Biol | Volume | 374 |
| Issue | 2 | Pages | 264-80 |
| PubMed ID | 23261932 | Mgi Jnum | J:193412 |
| Mgi Id | MGI:5468382 | Doi | 10.1016/j.ydbio.2012.12.007 |
| Citation | Wang Q, et al. (2013) The Xin repeat-containing protein, mXinbeta, initiates the maturation of the intercalated discs during postnatal heart development. Dev Biol 374(2):264-80 |
| abstractText | The intercalated disc (ICD) is a unique structure to the heart and plays vital roles in communication and signaling among cardiomyocytes. ICDs are formed and matured during postnatal development through a profound redistribution of the intercellular junctions, as well as recruitment and assembly of more than 200 proteins at the termini of cardiomyocytes. The molecular mechanism underlying this process is not completely understood. The mouse orthologs (mXinalpha and mXinbeta) of human cardiomyopathy-associated (CMYA)/Xin actin-binding repeat-containing protein (XIRP) genes (CMYA1/XIRP1 and CMYA3/XIRP2, respectively) encode proteins localized to ICDs. Ablation of mXinalpha results in adult late-onset cardiomyopathy with conduction defects and up-regulation of mXinbeta. ICD structural defects are found in adult but not juvenile mXinalpha-null hearts. On the other hand, loss of mXinbeta leads to ICD defects at postnatal day 16.5, a developmental stage when the heart is forming ICDs, suggesting mXinbeta is required for ICD formation. Using quantitative Western blot, we showed in this study that mXinbeta but not mXinalpha was uniquely up-regulated during the redistribution of intercellular junction from the lateral membrane of cardiomyocytes to their termini. In the absence of mXinbeta, the intercellular junctions failed to be restricted to the termini of the cells, and the onset of such defect correlated with the peak expression of mXinbeta. Immunofluorescence staining and subcellular fractionation showed that mXinbeta preferentially associated with the forming ICDs, further suggesting that mXinbeta functioned locally to promote ICD maturation. In contrast, the spatiotemporal expression profile of mXinalpha and the lack of more severe ICD defects in mXinalpha-/-;mXinbeta-/- double knockout hearts than in mXinbeta-/- hearts suggested that mXinalpha was not essential for the postnatal formation of ICDs. A two-step model for the development of ICD is proposed where mXinbeta is essential for the redistribution of intercellular junction components from the lateral puncta to the cell termini. |
