Journal article
The N-terminal tropomyosin- and actin-binding sites are important for leiomodin 2's function
Molecular biology of the cell, Vol.27(16), pp.2565-2575
08/15/2016
Handle:
https://hdl.handle.net/2376/106050
PMCID: PMC4985258
PMID: 27307584
Abstract
Leiomodin 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.
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Details
- Title
- The N-terminal tropomyosin- and actin-binding sites are important for leiomodin 2's function
- Creators
- Thu Ly - Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164-6515Natalia Moroz - Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164-6515Christopher T Pappas - Department of Cellular and Molecular Medicine, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ 85721Stefanie M Novak - Department of Cellular and Molecular Medicine, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ 85721Dmitri Tolkatchev - Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164-6515Dayton Wooldridge - Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164-6515Rachel M Mayfield - Department of Cellular and Molecular Medicine, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ 85721Gregory Helms - Center for NMR Spectroscopy, Washington State University, Pullman, WA 99164-4630Carol C Gregorio - Department of Cellular and Molecular Medicine, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ 85721Alla S Kostyukova - Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164-6515 alla.kostyukova@wsu.edu
- Publication Details
- Molecular biology of the cell, Vol.27(16), pp.2565-2575
- Academic Unit
- Plant Pathology, Department of; Chemical Engineering and Bioengineering, School of
- Publisher
- United States
- Grant note
- R01 GM081688 / NIGMS NIH HHS T32 GM008336 / NIGMS NIH HHS R01 HL123078 / NHLBI NIH HHS R01 HL108625 / NHLBI NIH HHS F31 HL117520 / NHLBI NIH HHS
- Identifiers
- 99900546958501842
- Language
- English
- Resource Type
- Journal article