| First Author | Wang Q | Year | 2013 |
| Journal | Arch Biochem Biophys | Volume | 535 |
| Issue | 1 | Pages | 91-100 |
| PubMed ID | 23296090 | Mgi Jnum | J:206707 |
| Mgi Id | MGI:5551709 | Doi | 10.1016/j.abb.2012.12.018 |
| Citation | Wang Q, et al. (2013) Intercalated disc protein, mXinalpha, suppresses p120-catenin-induced branching phenotype via its interactions with p120-catenin and cortactin. Arch Biochem Biophys 535(1):91-100 |
| abstractText | The Xin repeat-containing proteins, Xinalpha (Xirp1) and Xinbeta (Xirp2), localize to the intercalated discs (ICDs) of mammalian hearts. Mouse Xinalpha (mXinalpha) directly interacts with beta-catenin and actin filaments, potentially coupling the N-cadherin/beta-catenin complexes to the underlying actin cytoskeleton and modulating ICD integrity and function. Supporting this possibility, mXinalpha-null hearts develop ICD structural defects and cardiomyopathy with conduction defects. However, the underlying mechanisms leading to these defects remain unclear. Here, we showed that mXinalpha also interacted with p120-catenin and cortactin. Different from the beta-catenin binding domain, there existed multiple p120-catenin binding sites on mXinalpha, while only the extreme N-terminus of mXinalpha containing a SH3-binding motif could interact with cortactin. In mouse heart, a significant fraction of cortactin was co-localized with N-cadherin to ICDs, whereas in mXinalpha-null heart, this fraction of cortactin was drastically reduced. Therefore, mXinalpha may modulate ICD integrity and function through its interactions with catenins and cortactin. Analyses of the in vivo consequence of p120-catenin and mXinalpha interaction revealed that force-expressed mXinalpha or its fragments significantly suppressed the p120-catenin-induced branching phenotypes. It is known that p120-catenin directly regulates Rho GTPases, leading to the branching phenotype. Thus, mXinalpha may sequester the p120-catenin from inhibiting RhoA activity and/or from activating Rac1 activity. |
