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Original Article |
Correspondence to: Siegfried Labeit, Klinikum Mannheim, Theodor-Kutzer-Ufer-1, Mannheim 68167, Germany. Tel:(49) 621-383-2422 Fax:(49) 621-383-1971 E-mail:labeit{at}embl-heidelberg.de.
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 
-actinin in vertebrate Z-lines. Myopalladin's nebulin/nebulette and -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 -actinin and nebulin/nebulette) to those involved in muscle gene expression (via CARP).
Key Words:
-actinin, nebulin, palladin, myopalladin, CARP
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