Leiomodin-2 is an antagonist of tropomodulin-1 at the pointed end of the thin filaments in cardiac muscle

Takehiro Tsukada, Christopher T. Pappas, Natalia Moroz, Parker B Antin, Alla S. Kostyukova, Carol Gregorio

Research output: Contribution to journalArticle

55 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3136-3145
Number of pages10
JournalJournal of Cell Science
Volume123
Issue number18
DOIs
StatePublished - Sep 15 2010

Fingerprint

Tropomodulin
Myocardium
Actins
Striated Muscle
Microfilament Proteins
Actin Cytoskeleton
Cardiac Myocytes
Protein Isoforms
Proteins
Binding Sites

Keywords

  • Cardiomyocytes
  • Leiomodin
  • Lmod2
  • Thin filament
  • Tropomodulin
  • WH2 domain

ASJC Scopus subject areas

  • Cell Biology

Cite this

Leiomodin-2 is an antagonist of tropomodulin-1 at the pointed end of the thin filaments in cardiac muscle. / Tsukada, Takehiro; Pappas, Christopher T.; Moroz, Natalia; Antin, Parker B; Kostyukova, Alla S.; Gregorio, Carol.

In: Journal of Cell Science, Vol. 123, No. 18, 15.09.2010, p. 3136-3145.

Research output: Contribution to journalArticle

Tsukada, Takehiro ; Pappas, Christopher T. ; Moroz, Natalia ; Antin, Parker B ; Kostyukova, Alla S. ; Gregorio, Carol. / Leiomodin-2 is an antagonist of tropomodulin-1 at the pointed end of the thin filaments in cardiac muscle. In: Journal of Cell Science. 2010 ; Vol. 123, No. 18. pp. 3136-3145.
@article{9717feec25844bc4ac6f3435558a6d28,
title = "Leiomodin-2 is an antagonist of tropomodulin-1 at the pointed end of the thin filaments in cardiac muscle",
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.",
keywords = "Cardiomyocytes, Leiomodin, Lmod2, Thin filament, Tropomodulin, WH2 domain",
author = "Takehiro Tsukada and Pappas, {Christopher T.} and Natalia Moroz and Antin, {Parker B} and Kostyukova, {Alla S.} and Carol Gregorio",
year = "2010",
month = "9",
day = "15",
doi = "10.1242/jcs.071837",
language = "English (US)",
volume = "123",
pages = "3136--3145",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "18",

}

TY - JOUR

T1 - Leiomodin-2 is an antagonist of tropomodulin-1 at the pointed end of the thin filaments in cardiac muscle

AU - Tsukada, Takehiro

AU - Pappas, Christopher T.

AU - Moroz, Natalia

AU - Antin, Parker B

AU - Kostyukova, Alla S.

AU - Gregorio, Carol

PY - 2010/9/15

Y1 - 2010/9/15

N2 - 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.

AB - 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.

KW - Cardiomyocytes

KW - Leiomodin

KW - Lmod2

KW - Thin filament

KW - Tropomodulin

KW - WH2 domain

UR - http://www.scopus.com/inward/record.url?scp=77956930753&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956930753&partnerID=8YFLogxK

U2 - 10.1242/jcs.071837

DO - 10.1242/jcs.071837

M3 - Article

C2 - 20736303

AN - SCOPUS:77956930753

VL - 123

SP - 3136

EP - 3145

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 18

ER -