title: Essential roles of an intercalated disc protein, mXinbeta, in postnatal heart growth and survival.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Biology, University of Iowa, Iowa City, IA 52242-1324, USA.
authors.forename: Qinchuan
authors.initials: Q
authors.lastname: Wang
authors.forename: Jenny Li-Chun
authors.initials: JL
authors.lastname: Lin
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Reinking
authors.forename: Han-Zhong
authors.initials: HZ
authors.lastname: Feng
authors.forename: Fu-Chi
authors.initials: FC
authors.lastname: Chan
authors.forename: Cheng-I
authors.initials: CI
authors.lastname: Lin
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Jin
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Gustafson-Wagner
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Scholz
authors.forename: Baoli
authors.initials: B
authors.lastname: Yang
authors.forename: Jim Jung-Ching
authors.initials: JJ
authors.lastname: Lin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation; D002470:Cell Survival; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D006321:Heart / Q000254:growth & development* / Q000503:physiopathology*; D060588:LIM Domain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D009687:Nuclear Proteins; C500305:XIRP2 protein, mouse