Tissue-specific expression and α-actinin binding properties of the Z-disc titin: Implications for the nature of vertebrate Z-discs

H. Sorimachi, A. Freiburg, B. Kolmerer, S. Ishiura, G. Stier, C. C. Gregorio, D. Labeit, W. A. Linke, K. Suzuki, S. Labeit

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Abstract

Titins are giant filamentous proteins which connect Z-discs and M-lines in the sarcomeres of vertebrate striated muscles. Comparison of the N-terminal region of titin (Z-disc region) from different skeletal and cardiac muscles reveals a 900-residue segment which is expressed in different length variants, dependent on tissue type. When searching for ligands of this differentially expressed domain by a yeast-two hybrid approach, we detected binding to α-actinin. The isolated α-actinin cDNAs were derived from the C-terminal region of the α-actinin isoform (α-actinin-2) encoded by the ACTN2 gene. Therefore, the two antiparallel subunits of an α-actinin-2 homodimer will attach to actin at their respective C termini, whereas they will bind to the Z-disc titin at their N termini. This may thus explain how α-actinins can cross-link antiparallel titin and thin filaments from opposing sarcomeres. The α-actinin-2 binding site of the Z-disc titin is located within a sequence of 45-residue repeats, referred to as Z-repeat region. Both the N-terminal and C-terminal Z-repeats have α-actinin binding properties and are expressed in all striated muscles. By contrast, the more central Z-repeats are expressed in slow and fast skeletal muscles, as well as embryonic and adult cardiac muscles, in different copy numbers. Such alternative splicing of the Z-disc titin appears to be important for the tissue and fibre type diversity of the Z-disc lattice.

Original languageEnglish (US)
Pages (from-to)688-695
Number of pages8
JournalJournal of Molecular Biology
Volume270
Issue number5
DOIs
StatePublished - Aug 1 1997

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Keywords

  • Alpha-actinin
  • Alternative splicing
  • Striated and smooth muscles
  • Titin (connectin)
  • Z-discs

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Sorimachi, H., Freiburg, A., Kolmerer, B., Ishiura, S., Stier, G., Gregorio, C. C., Labeit, D., Linke, W. A., Suzuki, K., & Labeit, S. (1997). Tissue-specific expression and α-actinin binding properties of the Z-disc titin: Implications for the nature of vertebrate Z-discs. Journal of Molecular Biology, 270(5), 688-695. https://doi.org/10.1006/jmbi.1997.1145