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A comparative and phylogenetic analysis of the alpha-actinin rod domain
Umeå University, Faculty of Science and Technology, Chemistry.
Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:umu:diva-5547OAI: oai:DiVA.org:umu-5547DiVA: diva2:145093
Available from: 2006-11-16 Created: 2006-11-16 Last updated: 2010-01-13Bibliographically 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.
Keyword
alpha-actinin, evolution, spectrin repeat, intragene duplication, phylogenetic tree, spectrin superfamily
National Category
Biochemistry and Molecular Biology
Identifiers
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
Opponent
Supervisors
Available from: 2006-11-16 Created: 2006-11-16 Last updated: 2011-04-26Bibliographically approved

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