Intercalated disc protein Xinβ is required for Hippo-YAP signaling in the heart
| Basic data | |
|---|---|
| OCA1. Surname awarded to the assessed person | Kyselovič |
| OCA2. Name awarded to the assessed person | Ján |
| OCA3. Degrees awarded to the assessed person | Prof. , Pharm.D., CSc. |
| OCA4. Hyperlink to the entry of the person in the Register of university staff | https://www.portalvs.sk/regzam/detail/3738 |
| OCA5. Area of assessment | study programme pharmacy (joint study programme) · I. + II. degree |
| OCA6. Category of the research/artistic/other output | |
| OCA7. Year of publication of the research/artistic/other output | 2020 |
| OCA8. ID of the record in the Central Registry of Publication Activity (CRPA) or the Central Registry of Artistic Activity (CRAA) | 216126 |
| OCA9. Hyperlink to the record in CRPA or CRAA | https://app.crepc.sk/?fn=detailBiblioForm&sid=E4662E652762CF0C11672E6DEF |
| Characteristics of the output that is not registered in CRPA or CRAA | |
| OCA10. Hyperlink to the record in another publicly accessible register, catalogue of research/ artistic/other outputs | |
| OCA11. Characteristics of the output in the format of the CRPA or the CRAA bibliographic record, if the output is not available in a publicly accessible register or catalogue of outputs | Intercalated disc protein Xinβ is required for Hippo-YAP signaling in the heart |
| OCA12. Type of the output (if the output is not registered in CRPA or CRAA) | article |
| OCA13. Hyperlink to the webpage where the output is available (full text, other documentation, etc.) | |
| OCA14. Characteristics of the author's contribution | member of the international scientific team |
| OCA15. Annotation of the output with contextual information concerning the description of creative process and the content of the research/artistic/other activity, etc. | 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. |
| Other data | |
| OCA16. Annotation of the output in English | 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. |
| OCA17. List of maximum 5 most significant citations corresponding to the output | 2023: van Kampen, S.J. - Han, S.J. - van Ham, W.B. - Kyriakopoulou, E. - Stouthart, E.W. - Goversen, B. - Monshouwer-Kloots, J. - Perini, I. - de Ruiter, H. - van der Kraak, P. - Vink, A. - van Laake, L.W. - Groeneweg, J.A. - de Boer,T.P. - Tsui, H. - Boogerd, C.J. - van Veen, T.A.B. - van Rooij, E.: PITX2 induction leads to impaired cardiomyocyte function in arrhythmogenic cardiomyopathy. In: Stem Cell Reports, vol. 18, no. 3, 2023, s. 749-764 -- SCI ; SCOPUS 2023: Amoni, M. - Vermoortele, D. - Ekhteraei- Tousi, S. - Donate Puertas, R. - Gilbert, G. - Youness, M. - Thienpont, B. - Willems, R. - Roderick, H.L. - Claus, P. - Sipido, K.R.: Heterogeneity of Repolarization and Cell- CellVariability of Cardiomyocyte Remodeling Within the Myocardial Infarction Border Zone Contribute to Arrhythmia Susceptibility. In: Circulation: Arrhythmia and Electrophysiology, vol. 16, no. 5, 2023, art. no. e011677 -- SCI ; SCOPUS 2023: Pang, P. - Si, W. - Wu, H. - Wang, C. - Liu, K. - Jia, Y. - Zhang, Z. - Zhang, F. - Kong, X. - Yang, Y. - Jiang, W. - Song, J. - Zeng, L. - Xiong, Y. - Lian, J. - Wang, N. - Bian, Y. - Yang, B.: The circular RNA circHelzenhances cardiac fibrosis by facilitating the nuclear translocation of YAP1. In: Translational Research, vol. 257, 2023, s. 30-42 - - SCI ; SCOPUS 2024: Leng, J. - Wang, C. - Liang, Z. - Qiu, F. - Zhang, S. - Yang, Y.: An updated review of YAP: A promising therapeutic target against cardiac aging?. In: International Journal of Biological Macromolecules, vol. 254, 2024, art. no.127670 -- SCI ; SCOPUS 2023: Luo, A. - Jia, Y. - Hao, R. - Zhou, X. - Bao, C. - Yang, L. - Gu, C. - Tang, H. - Chu, A.A.: Proteomic and Phosphoproteomic Analysis of Right Ventricular Hypertrophy in the Pulmonary Hypertension Rat Model. In: Journal ofProteome Research, vol. 23, no. 1, 2024, s. 264- 276 -- SCI ; SCOPUS |
| OCA18. Characteristics of the output's impact on socio-economic practice | contribution of new knowledge to the issue |
| OCA19. Characteristics of the output and related activities' impact on the educational process | research in the field |