The N-terminal tropomyosin- and actin-binding sites are important for leiomodin 2's function.
Pappas, Christopher T
Novak, Stefanie M
Mayfield, Rachel M
Gregorio, Carol C
Kostyukova, Alla S
AffiliationUniv Arizona, Sarver Mol Cardiovasc Res Program, Dept Cellular & Mol Med
MetadataShow full item record
PublisherAMER SOC CELL BIOLOGY
CitationThe N-terminal tropomyosin- and actin-binding sites are important for leiomodin 2's function. 2016, 27 (16):2565-75 Mol. Biol. Cell
JournalMolecular biology of the cell
Rights© 2016 Ly, Moroz, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc -sa/3.0).
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractLeiomodin is a potent actin nucleator related to tropomodulin, a capping protein localized at the pointed end of the thin filaments. Mutations in leiomodin-3 are associated with lethal nemaline myopathy in humans, and leiomodin-2-knockout mice present with dilated cardiomyopathy. The arrangement of the N-terminal actin- and tropomyosin-binding sites in leiomodin is contradictory and functionally not well understood. Using one-dimensional nuclear magnetic resonance and the pointed-end actin polymerization assay, we find that leiomodin-2, a major cardiac isoform, has an N-terminal actin-binding site located within residues 43-90. Moreover, for the first time, we obtain evidence that there are additional interactions with actin within residues 124-201. Here we establish that leiomodin interacts with only one tropomyosin molecule, and this is the only site of interaction between leiomodin and tropomyosin. Introduction of mutations in both actin- and tropomyosin-binding sites of leiomodin affected its localization at the pointed ends of the thin filaments in cardiomyocytes. On the basis of our new findings, we propose a model in which leiomodin regulates actin poly-merization dynamics in myocytes by acting as a leaky cap at thin filament pointed ends.
VersionFinal published version
SponsorsNational Institutes of Health [RO1GM081688, R01HL108625, R01HL123078, 1F31HL117520]
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- Authors: Chereau D, Boczkowska M, Skwarek-Maruszewska A, Fujiwara I, Hayes DB, Rebowski G, Lappalainen P, Pollard TD, Dominguez R
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- Issue date: 2016 May
- Identification of residues within tropomodulin-1 responsible for its localization at the pointed ends of the actin filaments in cardiac myocytes.
- Authors: Tsukada T, Kotlyanskaya L, Huynh R, Desai B, Novak SM, Kajava AV, Gregorio CC, Kostyukova AS
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- Leiomodin-2 is an antagonist of tropomodulin-1 at the pointed end of the thin filaments in cardiac muscle.
- Authors: Tsukada T, Pappas CT, Moroz N, Antin PB, Kostyukova AS, Gregorio CC
- Issue date: 2010 Sep 15