Journal article
Essential Roles of an Intercalated Disc Protein, mXinβ, in Postnatal Heart Growth and Survival
Circulation research, Vol.106(9), pp.1468-U61
05/14/2010
DOI: 10.1161/CIRCRESAHA.109.212787
PMCID: PMC2872156
PMID: 20360251
Abstract
Rationale: The Xin repeat–containing proteins mXinα and mXinβ localize to the intercalated disc of mouse heart and are implicated in cardiac development and function. The mXinα directly interacts with β-catenin, p120-catenin, and actin filaments. Ablation of mXinα results in adult late-onset cardiomyopathy with conduction defects. An upregulation of the mXinβ in mXinα-deficient hearts suggests a partial compensation.
Objective: The essential roles of mXinβ in cardiac development and intercalated disc maturation were investigated.
Methods and Results: Ablation of mXinβ led to abnormal heart shape, ventricular septal defects, severe growth retardation, and postnatal lethality with no upregulation of the mXinα. Postnatal upregulation of mXinβ in wild-type hearts, as well as altered apoptosis and proliferation in mXinβ-null hearts, suggests that mXinβ is required for postnatal heart remodeling. The mXinβ-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 mXinβ resulted in the failure of forming mature intercalated discs and the mislocalization of mXinα and N-cadherin. The mXinβ-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 mXinβ in the intercalated disc maturation but also mechanisms of mXinβ modulating N-cadherin–mediated adhesion signaling and its crosstalk signaling for postnatal heart growth and animal survival.
Details
- Title: Subtitle
- Essential Roles of an Intercalated Disc Protein, mXinβ, in Postnatal Heart Growth and Survival
- Creators
- Qinchuan WangJenny Li-Chun LinBenjamin E. ReinkingHan-Zhong FengFu-Chi ChanCheng-I Lin - National Defense Medical CenterJian-Ping JinElisabeth A. Gustafson-WagnerThomas D. ScholzBaoli Yang - University of IowaJim Jung-Ching Lin
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.106(9), pp.1468-U61
- DOI
- 10.1161/CIRCRESAHA.109.212787
- PMID
- 20360251
- PMCID
- PMC2872156
- NLM abbreviation
- Circ Res
- ISSN
- 0009-7330
- Copyright
- 2010 © American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. The American Heart Association is qualified 501(c)(3) tax-exempt organization.
- Language
- English
- Date published
- 05/14/2010
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics; Biology; BioVentures Center; Obstetrics and Gynecology; Child and Community Health
- Record Identifier
- 9983557419502771
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