title: Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies.
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 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).
authors: European Molecular Biology Laboratory, Heidelberg 69117, Germany.
authors: M L
authors: ML
authors: Bang
authors: R E
authors: RE
authors: Mudry
authors: A S
authors: AS
authors: McElhinny
authors: K
authors: K
authors: Trombitás
authors: A J
authors: AJ
authors: Geach
authors: R
authors: R
authors: Yamasaki
authors: H
authors: H
authors: Sorimachi
authors: H
authors: H
authors: Granzier
authors: C C
authors: CC
authors: Gregorio
authors: S
authors: S
authors: Labeit
mesh_terms: D000185:Actinin / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D020832:EF Hand Motifs / Q000235:genetics; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D009687:Nuclear Proteins / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011817:Rabbits; D012097:Repressor Proteins / Q000378:metabolism; D012518:Sarcomeres / Q000378:metabolism* / Q000648:ultrastructure; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques
chemical_list: C491304:ANKRD1 protein, human; C104844:Ankrd1 protein, mouse; C426225:MYPN protein, human; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D000185:Actinin