• search hit 1 of 1
Back to Result List

Mena/VASP and alphaII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy

Please always quote using this URN: urn:nbn:de:bvb:20-opus-128760
  • Background: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzedBackground: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. Results: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. Conclusions: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: Peter M. Benz, Carla J. Merkel, Kristin Offner, Marco Abeßer, Melanie Ullrich, Tobias Fischer, Barbara Bayer, Helga Wagner, Stepan Gambaryan, Jeanine A. Ursitti, Ibrahim M. Adham, Wolfgang A. Linke, Stephan M. Feller, Ingrid Fleming, Thomas Renné, Stefan Frantz, Andreas Unger, Kai Schuh
URN:urn:nbn:de:bvb:20-opus-128760
Document Type:Journal article
Faculties:Medizinische Fakultät
Language:English
Parent Title (English):Cell Communication and Signaling
Year of Completion:2013
Volume:11
Issue:56
Source:Cell Communication and Signaling 2013, 11:56. doi:10.1186/1478-811X-11-56
DOI:https://doi.org/10.1186/1478-811X-11-56
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 571 Physiologie und verwandte Themen
Tag:Mena/VASP; actin; dilated cardiomyopathy; heart; spectrin
Release Date:2016/04/05
EU-Project number / Contract (GA) number:311575
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung