Thievessen, Ingo, Suhr, Frank ORCID: 0000-0002-9013-3944, Vergarajauregui, Silvia, Bottcher, Ralph T., Brixius, Klara, Rosenberger, Georg, Dewald, Oliver, Fleischmann, Bernd K., Ghanem, Alexander, Kruger, Marcus, Engel, Felix B., Fabry, Ben, Bloch, Wilhelm and Fassler, Reinhard (2022). The focal adhesion protein beta-parvin controls cardiomyocyte shape and sarcomere assembly in response to mechanical load. Curr. Biol., 32 (14). S. 3033 - 3058. CAMBRIDGE: CELL PRESS. ISSN 1879-0445

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Abstract

Physiological and pathological cardiac stress induced by exercise and hypertension, respectively, increase the hemodynamic load for the heart and trigger specific hypertrophic signals in cardiomyocytes leading to adaptive or maladaptive cardiac hypertrophy responses involving a mechanosensitive remodeling of the contractile cytoskeleton. Integrins sense load and have been implicated in cardiac hypertrophy, but how they discriminate between the two types of cardiac stress and translate mechanical loads into specific cytoskeletal signaling pathways is not clear Here, we report that the focal adhesion protein beta-parvin is highly expressed in cardiomyocytes and facilitates the formation of cell protrusions, the serial assembly of newly synthesized sarcomeres, and the hypertrophic growth of neonatal rat ventricular cardiomyocytes (NRVCs) in vitro. In addition, physiological mechanical loading of NRVCs by either the application of cyclic, uni-axial stretch, or culture on physiologically stiff substrates promotes NRVC elongation in a beta-parvin-dependent manner, which is achieved by binding of beta-parvin to alpha/beta-PIX, which in turn activates Rac1. Importantly, loss-of-function studies in mice also revealed that beta-parvin is essential for the exercise-induced cardiac hypertrophy response in vivo. Our results identify beta-parvin as a novel mechano-responsive signaling hub in hypertrophic cardiomyocytes that drives cell elongation in response to physiological mechanical loads.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Thievessen, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suhr, FrankUNSPECIFIEDorcid.org/0000-0002-9013-3944UNSPECIFIED
Vergarajauregui, SilviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bottcher, Ralph T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brixius, KlaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenberger, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dewald, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fleischmann, Bernd K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ghanem, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kruger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engel, Felix B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fabry, BenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bloch, WilhelmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fassler, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-691646
DOI: 10.1016/j.cub.2022.05.047
Journal or Publication Title: Curr. Biol.
Volume: 32
Number: 14
Page Range: S. 3033 - 3058
Date: 2022
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1879-0445
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INTEGRIN-LINKED KINASE; MYOCYTE-SPECIFIC EXCISION; RAT VENTRICULAR MYOCYTES; PRESSURE-OVERLOAD; CARDIAC-HYPERTROPHY; MEMBRANE PROTRUSIONS; CELL MORPHOLOGY; HEART-FAILURE; ALPHA-PIX; ILKMultiple languages
Biochemistry & Molecular Biology; Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69164

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