Intercalated disc protein, mXinα, suppresses p120-catenin-induced branching phenotype via its interactions with p120-catenin and cortactin

Qinchuan Wang, Te Ling Lu, Eric Adams, Jenny Li Chun Lin, Jim Jung Ching Lin

Research output: Contribution to journalArticlepeer-review

Abstract

The Xin repeat-containing proteins, Xinα (Xirp1) and Xinβ (Xirp2), localize to the intercalated discs (ICDs) of mammalian hearts. Mouse Xinα (mXinα) directly interacts with β-catenin and actin filaments, potentially coupling the N-cadherin/β-catenin complexes to the underlying actin cytoskeleton and modulating ICD integrity and function. Supporting this possibility, mXinα-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 mXinα also interacted with p120-catenin and cortactin. Different from the β-catenin binding domain, there existed multiple p120-catenin binding sites on mXinα, while only the extreme N-terminus of mXinα 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 mXinα-null heart, this fraction of cortactin was drastically reduced. Therefore, mXinα may modulate ICD integrity and function through its interactions with catenins and cortactin. Analyses of the in vivo consequence of p120-catenin and mXinα interaction revealed that force-expressed mXinα 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, mXinα may sequester the p120-catenin from inhibiting RhoA activity and/or from activating Rac1 activity.

Original languageEnglish (US)
Pages (from-to)91-100
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume535
Issue number1
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

Keywords

  • Branching phenotype
  • Cortactin
  • Intercalated disc
  • N-cadherin
  • XIRP
  • mXin
  • p120-catenin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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