Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies.
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 alpha-actinin in vertebrate Z-lines. Myopalladin's nebulin/nebulette and alpha-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 NH(2)-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 NH(2)-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 alpha-actinin and nebulin/nebulette) to those involved in muscle gene expression (via CARP).
Mesh Terms:
Actinin, Amino Acid Sequence, Animals, Blotting, Northern, Cells, Cultured, EF Hand Motifs, Humans, Mice, Microscopy, Fluorescence, Molecular Sequence Data, Muscle Proteins, Muscle, Skeletal, Myocardium, Nuclear Proteins, Phylogeny, Protein Binding, Protein Structure, Tertiary, Rabbits, Repressor Proteins, Sarcomeres, Sequence Alignment, Two-Hybrid System Techniques
Actinin, Amino Acid Sequence, Animals, Blotting, Northern, Cells, Cultured, EF Hand Motifs, Humans, Mice, Microscopy, Fluorescence, Molecular Sequence Data, Muscle Proteins, Muscle, Skeletal, Myocardium, Nuclear Proteins, Phylogeny, Protein Binding, Protein Structure, Tertiary, Rabbits, Repressor Proteins, Sarcomeres, Sequence Alignment, Two-Hybrid System Techniques
J. Cell Biol.
Date: Apr. 16, 2001
PubMed ID: 11309420
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