Dimerization of the cardiac ankyrin protein CARP

Implications for MARP titin-based signaling

Stephanie H. Witt, Dietmar Labeit, Hendrikus "Henk" Granzier, Siegfried Labeit, Christian C. Witt

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)401-408
Number of pages8
JournalJournal of Muscle Research and Cell Motility
Volume26
Issue number6-8
DOIs
StatePublished - Dec 2005
Externally publishedYes

Fingerprint

Ankyrin Repeat
Ankyrins
Connectin
Dimerization
Muscle Proteins
Proteins
Yeast
Muscle
Two-Hybrid System Techniques
Hybrid systems
Dimers
Genes
Muscles
Desmin
Muscular Dystrophies
Escherichia coli Proteins
Protein Subunits
Escherichia coli
Gel Chromatography

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Dimerization of the cardiac ankyrin protein CARP : Implications for MARP titin-based signaling. / Witt, Stephanie H.; Labeit, Dietmar; Granzier, Hendrikus "Henk"; Labeit, Siegfried; Witt, Christian C.

In: Journal of Muscle Research and Cell Motility, Vol. 26, No. 6-8, 12.2005, p. 401-408.

Research output: Contribution to journalArticle

Witt, Stephanie H. ; Labeit, Dietmar ; Granzier, Hendrikus "Henk" ; Labeit, Siegfried ; Witt, Christian C. / Dimerization of the cardiac ankyrin protein CARP : Implications for MARP titin-based signaling. In: Journal of Muscle Research and Cell Motility. 2005 ; Vol. 26, No. 6-8. pp. 401-408.
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