Disruption of cardiac Ena-VASP protein localization in intercalated disks causes dilated cardiomyopathy
, , , , , , , , , , , , and .
Am J Physiol Heart Circ Physiol 285 (6): H2471-81 (December 2003)Eigenthaler, Martin Engelhardt, Stefan Schinke, Birgitta Kobsar, Anna Schmitteckert, Eva Gambaryan, Stepan Engelhardt, Catherine M Krenn, Veit Eliava, Marina Jarchau, Thomas Lohse, Martin J Walter, Ulrich Hein, Lutz Research Support, Non-U.S. Gov't United States American journal of physiology. Heart and circulatory physiology Am J Physiol Heart Circ Physiol. 2003 Dec;285(6):H2471-81. Epub 2003 Aug 21..

Vasodilator-stimulated phosphoprotein (VASP) and mammalian enabled (Mena) are actin cytoskeleton and signaling modulators. Ena-VASP proteins share an identical domain organization with an NH2-terminal Ena VASP homology (EVH1) domain, which mediates the binding of these proteins to FPPPP-motif containing partners such as zyxin and vinculin. VASP and Mena are abundantly expressed in the heart. However, previous studies showed that disruption by gene targeting of VASP or Mena genes in mice did not reveal any cardiac phenotype, whereas mice lacking both VASP and Mena died during embryonic development. To determine the in vivo function of Ena-VASP proteins in the heart, we used a dominant negative strategy with cardiac-specific expression of the VASP-EVH1 domain. Transgenic mice with cardiac myocyte-restricted, alpha-myosin heavy chain promoter-directed expression of the VASP-EVH1 domain were generated. Overexpression of the EVH1 domain resulted in specific displacement of both VASP and Mena from cardiac intercalated disks. VASP-EVH1 transgenic mice developed dilated cardiomyopathy with myocyte hypertrophy and bradycardia, which resulted in early postnatal lethality in mice with high levels of transgene expression. The results demonstrate that Ena-VASP proteins may play an important role in intercalated disk function at the interface between cardiac myocytes.
  • @pharmawuerz
This publication has not been reviewed yet.

rating distribution
average user rating0.0 out of 5.0 based on 0 reviews
    Please log in to take part in the discussion (add own reviews or comments).