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Intercalated disc protein Xinβ is required for Hippo-YAP signaling in the heart
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-11 (2020), Nature Communications
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group, 2020.
-
Abstract
- Intercalated discs (ICD), specific cell-to-cell contacts that connect adjacent cardiomyocytes, ensure mechanical and electrochemical coupling during contraction of the heart. Mutations in genes encoding ICD components are linked to cardiovascular diseases. Here, we show that loss of Xinβ, a newly-identified component of ICDs, results in cardiomyocyte proliferation defects and cardiomyopathy. We uncovered a role for Xinβ in signaling via the Hippo-YAP pathway by recruiting NF2 to the ICD to modulate cardiac function. In Xinβ mutant hearts levels of phosphorylated NF2 are substantially reduced, suggesting an impairment of Hippo-YAP signaling. Cardiac-specific overexpression of YAP rescues cardiac defects in Xinβ knock-out mice—indicating a functional and genetic interaction between Xinβ and YAP. Our study reveals a molecular mechanism by which cardiac-expressed intercalated disc protein Xinβ modulates Hippo-YAP signaling to control heart development and cardiac function in a tissue specific manner. Consequently, this pathway may represent a therapeutic target for the treatment of cardiovascular diseases.<br />Intercalated discs ensure mechanical and electrochemical coupling during contraction of the heart. Here, the authors show that loss of Xinβ results in cardiomyocyte proliferation defects and cardiomyopathy by influencing the Hippo-YAP signalling pathway, thus affecting cardiac development and function.
- Subjects :
- Male
0301 basic medicine
Cardiomyopathy
General Physics and Astronomy
Cell Cycle Proteins
Cell Communication
030204 cardiovascular system & hematology
0302 clinical medicine
Myocyte
Myocytes, Cardiac
lcsh:Science
Mice, Knockout
Neurofibromin 2
Multidisciplinary
Heart development
Chemistry
Gene Expression Regulation, Developmental
Nuclear Proteins
Signal transducing adaptor protein
LIM Domain Proteins
Cell biology
DNA-Binding Proteins
medicine.anatomical_structure
Phosphorylation
Female
Signal transduction
Intercalated disc
Signal Transduction
Cell signalling
Cardiomyopathy, Dilated
Cell signaling
Science
Heart Ventricles
Protein Serine-Threonine Kinases
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
medicine
Animals
Hippo Signaling Pathway
Adaptor Proteins, Signal Transducing
Cell Proliferation
YAP-Signaling Proteins
General Chemistry
medicine.disease
Cardiovascular biology
Mice, Inbred C57BL
Cytoskeletal Proteins
030104 developmental biology
Mutation
lcsh:Q
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....aad20cffb5ab62e82d32c2b24f334d96