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

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 vari...

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Bibliographic Details
Published in:Journal of molecular biology 1997-08, Vol.270 (5), p.688-695
Main Authors: Sorimachi, H, Freiburg, A, Kolmerer, B, Ishiura, S, Stier, G, Gregorio, C.C, Labeit, D, Linke, W.A, Suzuki, K, Labeit, S
Format: Article
Language:English
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Summary: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.
ISSN:0022-2836
1089-8638
DOI:10.1006/jmbi.1997.1145