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Journal of Muscle Research & Cell Motility

, Volume 26, Issue 6–8, pp 401–408 | Cite as

Dimerization of the cardiac ankyrin protein CARP: Implications for MARP titin-based signaling

  • Stephanie H. Witt
  • Dietmar Labeit
  • Henk Granzier
  • Siegfried Labeit
  • Christian C. Witt
Article

Abstract

Cardiac ankyrin repeat protein (CARP) and its two close homologs ankrd2 (Arpp) and DARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). All three genes respond to a variety of stress/strain injury signals with their cytokine-like induction and can associate with the elastic region of titin/connectin. Recently, both CARP and ankrd2 were observed to be elevated in cardiac diseases as well as muscular dystrophies, implicating their joined signaling in muscle diseases. Here we show that CARP in the yeast two-hybrid system (YTH) interacts with itself and desmin. To further verify the YTH data and to investigate possible CARP subunit structure(s), we expressed CARP in E. coli. Expressed CARP has an apparent mobility of about 70 kDa on gel filtration, corresponding to a dimeric species. Yeast two-hybrid experiments using amino- and carboxyterminal deletion clones suggest that CARP, ankrd2, and DARP contain potential coiled-coil dimerization motifs within their unique aminoterminal domains that mediate the formation of homo-dimers. In contrast, we could not detect the formation of hetero-dimers between CARP, ankrd2, and DARP. Therefore, when CARP, ankrd2 and DARP are upregulated in disease/stress states, they are likely to be sorted into distinct structural protein complexes since CARP within the MARP family contains a unique aminoterminal dimerization motif.

Keywords

Muscular Dystrophy Ankyrin Repeat Congenital Muscular Dystrophy Limb Girdle Muscular Dystrophy Cardiac Ankyrin Repeat Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Notes

Acknowledgements

The authors would like to thank Richard Carmouche from the EMBL gene core for expert technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft (LA668/7-2 to SL and LA1969/1-1 to DL).

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Stephanie H. Witt
    • 1
  • Dietmar Labeit
    • 1
  • Henk Granzier
    • 2
  • Siegfried Labeit
    • 1
  • Christian C. Witt
    • 1
  1. 1.Institut für Anaesthesiologie und Operative IntensivmedizinUniversitätsklinikum MannheimMannheimGermany
  2. 2.Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology Washington State UniversityPullmanUSA

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