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Arginyltransferase regulates alpha cardiac actin function, myofibril formation and contractility during heart development

Academic Article
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Overview

authors

  • Rai, R.
  • Wong, C. C. L.
  • Xu, T.
  • Leu, N. A.
  • Dong, D. W. W.
  • Guo, C. Y.
  • McLaughlin, K. J.
  • Yates III, John
  • Kashina, A.

publication date

  • 2008

journal

  • Development  Journal

abstract

  • Post-translational arginylation mediated by arginyltransferase (Ate1) is essential for cardiovascular development and angiogenesis in mammals and directly affects myocardium structure in the developing heart. We recently showed that arginylation exerts a number of intracellular effects by modifying proteins involved in the functioning of the actin cytoskeleton and in cell motility. Here, we investigated the role of arginylation in the development and function of cardiac myocytes and their actin-containing structures during embryogenesis. Biochemical and mass spectrometry analyses showed that alpha cardiac actin undergoes arginylation at four sites during development. Ultrastructural analysis of the myofibrils in wild-type and Ate1 knockout mouse hearts showed that the absence of arginylation results in defects in myofibril structure that delay their development and affect the continuity of myofibrils throughout the heart, predicting defects in cardiac contractility. Comparison of cardiac myocytes derived from wild-type and Ate1 knockout mouse embryos revealed that the absence of arginylation results in abnormal beating patterns. Our results demonstrate cell-autonomous cardiac myocyte defects in arginylation knockout mice that lead to severe congenital abnormalities similar to those observed in human disease, and outline a new function of arginylation in the regulation of the actin cytoskeleton in cardiac myocytes.

subject areas

  • Actins
  • Aminoacyltransferases
  • Animals
  • Arginine
  • Cells, Cultured
  • Heart
  • Mice
  • Mice, Knockout
  • Models, Cardiovascular
  • Myocardial Contraction
  • Myocardium
  • Myocytes, Cardiac
  • Myofibrils
  • Protein Structure, Secondary
  • Sarcomeres
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Identity

PubMed Central ID

  • PMC2582055

International Standard Serial Number (ISSN)

  • 0950-1991

Digital Object Identifier (DOI)

  • 10.1242/dev.022723

PubMed ID

  • 18948421
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Additional Document Info

start page

  • 3881

end page

  • 3889

volume

  • 135

issue

  • 23

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