Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies

Marie Louise Bang, Ryan E. Mudry, Abigail S. McElhinny, Karoly Trombitás, Adam J. Geach, Rob Yamasaki, Hiroyuki Sorimachi, Hendrikus "Henk" Granzier, Carol Gregorio, Siegfried Labeit

Research output: Contribution to journalArticle

197 Scopus citations

Abstract

We describe here a novel sarcomeric 145-kD protein, myopalladin, which tethers together the COOH-terminal Src homology 3 domains of nebulin and nebulette with the EF hand motifs of α-actinin in vertebrate Z-lines. Myopalladin's nebulin/nebulette and α-actinin-binding sites are contained in two distinct regions within its COOH-terminal 90-kD domain. Both sites are highly homologous with those found in palladin, a protein described recently required for actin cytoskeletal assembly (Parast, M.M., and C.A. Otey. 2000. J. Cell Biol. 150:643-656). This suggests that palladin and myopalladin may have conserved roles in stress fiber and Z-line assembly. The NH2-terminal region of myopalladin specifically binds to the cardiac ankyrin repeat protein (CARP), a nuclear protein involved in control of muscle gene expression. Immunofluorescence and immunoelectron microscopy studies revealed that myopalladin also colocalized with CARP in the central I-band of striated muscle sarcomeres. Overexpression of myopalladin's NH2-terminal CARP-binding region in live cardiac myocytes resulted in severe disruption of all sarcomeric components studied, suggesting that the myopalladin-CARP complex in the central I-band may have an important regulatory role in maintaining sarcomeric integrity. Our data also suggest that myopalladin may link regulatory mechanisms involved in Z-line structure (via α-actinin and nebulin/nebulette) to those involved in muscle gene expression (via CARP).

Original languageEnglish (US)
Pages (from-to)413-427
Number of pages15
JournalJournal of Cell Biology
Volume153
Issue number2
DOIs
Publication statusPublished - Apr 16 2001

    Fingerprint

Keywords

  • α-actinin
  • CARP
  • Myopalladin
  • Nebulin
  • Palladin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Bang, M. L., Mudry, R. E., McElhinny, A. S., Trombitás, K., Geach, A. J., Yamasaki, R., ... Labeit, S. (2001). Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies. Journal of Cell Biology, 153(2), 413-427. https://doi.org/10.1083/jcb.153.2.413