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

195 Citations (Scopus)

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
StatePublished - Apr 16 2001

Fingerprint

Ankyrin Repeat
Actinin
Proteins
EF Hand Motifs
Gene Expression
Muscles
Stress Fibers
Sarcomeres
src Homology Domains
Striated Muscle
Immunoelectron Microscopy
Nuclear Proteins
Fluorescence Microscopy
Cardiac Myocytes
Protein Binding
Vertebrates
Actins
Binding Sites
nebulin

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

Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies. / Bang, Marie Louise; Mudry, Ryan E.; McElhinny, Abigail S.; Trombitás, Karoly; Geach, Adam J.; Yamasaki, Rob; Sorimachi, Hiroyuki; Granzier, Hendrikus "Henk"; Gregorio, Carol; Labeit, Siegfried.

In: Journal of Cell Biology, Vol. 153, No. 2, 16.04.2001, p. 413-427.

Research output: Contribution to journalArticle

Bang, ML, Mudry, RE, McElhinny, AS, Trombitás, K, Geach, AJ, Yamasaki, R, Sorimachi, H, Granzier, HH, Gregorio, C & 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, vol. 153, no. 2, pp. 413-427. https://doi.org/10.1083/jcb.153.2.413
Bang, Marie Louise ; Mudry, Ryan E. ; McElhinny, Abigail S. ; Trombitás, Karoly ; Geach, Adam J. ; Yamasaki, Rob ; Sorimachi, Hiroyuki ; Granzier, Hendrikus "Henk" ; Gregorio, Carol ; Labeit, Siegfried. / Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies. In: Journal of Cell Biology. 2001 ; Vol. 153, No. 2. pp. 413-427.
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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).",
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