NDLI: α-Actinin-2 deficiency results in sarcomeric defects in zebrafish that cannot be rescued by α-actinin-3 revealing functional differences between sarcomeric isoforms

Content Provider	PubMed Central
Author	Gupta, Vandana Discenza, Marie Guyon, Jeffrey R. Kunkel, Louis M. Beggs, Alan H.
Copyright Year	2012
Abstract	α-Actinins are actin-binding proteins that can be broadly divided into Ca2+-sensitive cytoskeletal and Ca2+-insensitive sarcomeric isoforms. To date, little is known about functional differences between the isoforms due to their indistinguishable activities in most in vitro assays. To identify functional differences in vivo between sarcomeric isoforms, we employed computational and molecular approaches to characterize the zebrafish (Danio rerio) genome, which contains orthologoues of each human α-actinin gene, including duplicated copies of actn3. Each isoform exhibits a distinct and unique pattern of gene expression as assessed by mRNA in situ hybridization, largely sharing similar expression profiles as seen in humans. The spatial conservation of expression of these genes from lower invertebrates to humans suggests that regulation and subsequent functions of these genes are conserved during evolution. Morpholino-based knockdown of the sarcomeric isoform, actn2, leads to skeletal muscle, cardiac, and ocular defects evident over the first week of development. Remarkably, despite the high degree of sequence conservation between actn2 and actn3, the phenotypes of α-actinin-2 deficient zebrafish can be rescued by overexpression of α-actinin-2 but not by α-actinin-3 mRNAs from zebrafish or human. These data provide functional evidence that the primary sequences of α-actinin-2 and α-actinin-3 evolved differences to optimize their functions.—Gupta, V., Discenza, M., Guyon, J. R., Kunkel, L. M., Beggs, A. H. α-Actinin-2 deficiency results in sarcomeric defects in zebrafish that cannot be rescued by α-actinin-3 revealing functional differences between sarcomeric isoforms.
Related Links	http://dx.doi.org/10.1096/fj.11-194548
Ending Page	1908
Page Count	17
Starting Page	1892
File Format	PDF
ISSN	08926638
e-ISSN	15306860
Journal	The FASEB Journal
Issue Number	5
Volume Number	26
Language	English
Publisher	Federation of American Societies for Experimental Biology
Publisher Date	2012-05-01
Access Restriction	Open
Rights Holder	Federation of American Societies for Experimental Biology
Subject Keyword	Biotechnology Genetics Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine Molecular Biology Biochemistry Biotechnology

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