Format

Send to

Choose Destination
Development. 2008 Dec;135(23):3881-9. doi: 10.1242/dev.022723. Epub 2008 Oct 23.

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

Author information

1
Department of Animal Biology and School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Erratum in

  • Development. 2008 Dec;135(23):3971.

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.

PMID:
18948421
PMCID:
PMC2582055
DOI:
10.1242/dev.022723
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center