Document Detail


α-Actinin2 is required for the lateral alignment of Z discs and ventricular chamber enlargement during zebrafish cardiogenesis.
MedLine Citation:
PMID:  22767232     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
α-Actinin2 (Actn2) is a predominant protein in the sarcomere Z disc whose mutation can lead to cardiomyopathy. However, the function of Actn2 in Z-disc assembly and cardiomyopathy in vertebrates remains elusive. We leveraged genetic tools in zebrafish embryos to elucidate the function of Actn2. We identified a single Actn2 homologue expressed in the zebrafish heart and conducted loss-of-function studies by antisense morpholino technology. Although zebrafish Actn2 assembles early into the Z disc, depletion of actn2 did not affect the early steps of sarcomere assembly. Instead, Actn2 is required for Z bodies to register laterally, forming well-aligned Z discs. Presumably as a consequence to this structural defect in the sarcomere, the depletion of Actn2 resulted in reduced cardiac function, primarily characterized as a reduced end-diastolic diameter. The depletion of actn2 also significantly reduced the ventricle chamber size, due to both reduced cardiomyocyte (CM) size and CM number. Interestingly, reduced CM size can be rescued by the cessation of heart contractions. The genetic studies of zebrafish uncovered a function for actn2 in lateral registration of Z body. In actn2 morphant fish, the Z-disc defect sequentially affects cardiac function, which leads to morphological changes in the ventricle through a mechanical force-dependent mechanism.
Authors:
Jingchun Yang; Xiaolei Xu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-05
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  26     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2012-12-12     Revised Date:  2013-10-11    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4230-42     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905, USA.
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MeSH Terms
Descriptor/Qualifier:
Actinin / genetics,  metabolism*
Animals
Blotting, Western
Heart / embryology*
In Situ Hybridization
In Situ Nick-End Labeling
Microscopy, Electron, Transmission
Muscle Development / genetics,  physiology
Myocardial Contraction / genetics,  physiology
Myocytes, Cardiac / cytology,  metabolism
Organogenesis / genetics,  physiology*
Reverse Transcriptase Polymerase Chain Reaction
Zebrafish
Zebrafish Proteins / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
HL81753/HL/NHLBI NIH HHS; R01 HL081753/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Zebrafish Proteins; 11003-00-2/Actinin
Comments/Corrections

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