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Molecular evolution and structure of α-actinin
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
2004 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 21, no 6, 1024-1031 p.Article in journal (Refereed) Published
Abstract [en]

The N-terminal actin-binding domain of -actinin is connected to the C-terminal EF-hands by a rod domain. Because of its ability to form dimers, -actinin can cross-link actin filaments in muscle cells as well as in nonmuscle cells. In the prototypic -actinins, the rod domain contains four triple helical bundles, or so-called spectrin repeats. We have found some atypical -actinins in early diverging organisms, such as protozoa and yeast, where the rod domain contains one and two spectrin repeats, respectively. This implies that the four repeats present in modern -actinins arose after two consecutive intragenic duplications from an -actinin with a single repeat. Further, the evolutionary gene tree of -actinins shows that the appearance of four distinct -actinin isoforms may have occurred after the vertebrate-invertebrate split. The topology of the tree lends support to the hypothesis that two rounds (2R) of genome duplication occurred early in the vertebrate radiation. The phylogeny also considers these atypical isoforms as the most basal to -actinins of vertebrates and other eukaryotes. The analysis also positioned -actinin of the fungi Encephalitozoo cuniculi close to the protozoa, supporting the suggestion that microsporidia are early eukaryotes. Because -actinin is considered the basal member of the spectrin family, our studies will improve the understanding of the origin and evolution of this superfamily.

Place, publisher, year, edition, pages
Chicago: Univ. of Chicago Press , 2004. Vol. 21, no 6, 1024-1031 p.
Keyword [en]
alfa-actinin, phylogeny, evolution, spectrin superfamily, spectrin repeat
URN: urn:nbn:se:umu:diva-14782DOI: doi:10.1093/molbev/msh094OAI: diva2:154454
Available from: 2007-06-18 Created: 2007-06-18 Last updated: 2011-04-26Bibliographically approved
In thesis
1. Molecular characterization and evolution of alpha-actinin: from protozoa to vertebrates
Open this publication in new window or tab >>Molecular characterization and evolution of alpha-actinin: from protozoa to vertebrates
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

alpha-actinin is a ubiquitous protein found in most eukaryotic organisms. The ability to form dimers allows alpha-actinin to cross-link actin in different structures. In muscle cells alpha-actinin is found at the Z-disk of sarcomeres. In non-muscle cells alpha-actinin is found in zonula adherens or focal adhesion sites where it can bind actin to the plasma membrane.

alpha-actinin is the shortest member of the spectrin superfamily of proteins which also includes spectrin, dystrophin and utrophin. Several hypotheses suggest that alpha-actinin is the ancestor of this superfamily.

The structure of alpha-actinin in higher organisms has been well characterized consisting of three main domains: an N-terminal actin-binding domain with two calponin homology domains, a central rod domain with four spectrin repeats and a C-terminal calcium-binding domain. Data mining of genomes from diverse organisms has made possible the discovery of new and atypical alpha-actinin isoforms that have not been characterized yet.

Invertebrates contain a single alpha-actinin isoform, whereas most of the vertebrates contain four. These four isoforms can be broadly classified in two groups, muscle isoforms and non-muscle isoforms. Muscle isoforms bind actin in a calcium independent manner whereas non-muscle isoforms bind actin in a calcium-dependent manner.

Some of the protozoa and fungi isoforms are atypical in that they contain fewer spectrin repeats in the rod domain. We have purified and characterized two ancestral alpha-actinins from the parasite Entamoeba histolytica. Our results show that despite the shorter rod domain they conserve the most important functions of modern alpha-actinin such as actin-bundling formation and calcium-binding regulation. Therefore it is suggested that they are genuine alpha-actinins.

The phylogenetic tree of alpha-actinin shows that the four different alpha-actinin isoforms appeared after the vertebrate-invertebrate split as a result of two rounds of genome duplication. The atypical alpha-actinin isoforms are placed as the most divergent isoforms suggesting that they are ancestral isoforms. We also propose that the most ancestral alpha-actinin contained a single repeat in its rod domain. After a first intragene duplication alpha-actinin with two spectrin repeats were created and a second intragene duplication gave rise to modern alpha-actinins with four spectrin repeats.

Place, publisher, year, edition, pages
Umeå: Kemi, 2006. 52 p.
alpha-actinin, evolution, spectrin repeat, intragene duplication, phylogenetic tree, spectrin superfamily
National Category
Biochemistry and Molecular Biology
urn:nbn:se:umu:diva-931 (URN)91-7264-204-1 (ISBN)
Public defence
2006-12-09, KB3A9, KBC, Umeå University SE-901 87, Umeå Sweden, 10:00
Available from: 2006-11-16 Created: 2006-11-16 Last updated: 2011-04-26Bibliographically approved

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