Journal article
Leiomodin-2 is an antagonist of tropomodulin-1 at the pointed end of the thin filaments in cardiac muscle
Journal of cell science, Vol.123(18), pp.3136-3145
09/15/2010
Handle:
https://hdl.handle.net/2376/104083
PMCID: PMC2931607
PMID: 20736303
Abstract
Regulation of actin filament assembly is essential for efficient contractile activity in striated muscle. Leiomodin is an actin-binding protein and homolog of the pointed-end capping protein, tropomodulin. These proteins are structurally similar, sharing a common domain organization that includes two actin-binding sites. Leiomodin also contains a unique C-terminal extension that has a third actin-binding WH2 domain. Recently, the striated-muscle-specific isoform of leiomodin (Lmod2) was reported to be an actin nucleator in cardiomyocytes. Here, we have identified a function of Lmod2 in the regulation of thin filament lengths. We show that Lmod2 localizes to the pointed ends of thin filaments, where it competes for binding with tropomodulin-1 (Tmod1). Overexpression of Lmod2 results in loss of Tmod1 assembly and elongation of the thin filaments from their pointed ends. The Lmod2 WH2 domain is required for lengthening because its removal results in a molecule that caps the pointed ends similarly to Tmod1. Furthermore, Lmod2 transcripts are first detected in the heart after it has begun to beat, suggesting that the primary function of Lmod2 is to maintain thin filament lengths in the mature heart. Thus, Lmod2 antagonizes the function of Tmod1, and together, these molecules might fine-tune thin filament lengths.
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Details
- Title
- Leiomodin-2 is an antagonist of tropomodulin-1 at the pointed end of the thin filaments in cardiac muscle
- Creators
- Takehiro Tsukada - Department of Cell Biology and Anatomy, and Sarver Molecular Cardiovascular Research Program, University of ArizonaChristopher T Pappas - Department of Cell Biology and Anatomy, and Sarver Molecular Cardiovascular Research Program, University of ArizonaNatalia Moroz - Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, UMDNJParker B Antin - Department of Cell Biology and Anatomy, and Sarver Molecular Cardiovascular Research Program, University of ArizonaAlla S Kostyukova - Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, UMDNJCarol C Gregorio - Department of Cell Biology and Anatomy, and Sarver Molecular Cardiovascular Research Program, University of Arizona
- Publication Details
- Journal of cell science, Vol.123(18), pp.3136-3145
- Academic Unit
- Plant Pathology, Department of; Chemical Engineering and Bioengineering, School of
- Publisher
- Company of Biologists
- Identifiers
- 99900546811301842
- Language
- English
- Resource Type
- Journal article