TISSUE-SPECIFIC EXPRESSION AND ALPHA-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-line s 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 d ifferent 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 alpha-actinin. The isolated alpha-ac tinin cDNAs were derived from the C-terminal region of the alpha-actin in isoform (alpha actinin-2) encoded by the ACTN2 gene. Therefore, the two antiparallel subunits of an alpha-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 alpha-acti nins can cross-link antiparallel titin and thin filaments from opposin g sarcomeres. The alpha-actinin-2 binding site of the Z-disc titin is located within a sequence of 45-residue repeats, referred to as Z-repe at region. Both the N-terminal and C-terminal Z-repeats have alpha-act inin binding properties and are expressed in all striated muscles. By contrast, the more central Z-repeats are expressed in slow and fast sk eletal muscles, as well as embryonic and adult cardiac muscles, in dif ferent copy numbers. Such alternative splicing of the Z-disc titin app ears to be important for the tissue and fibre type diversity of the Z- disc lattice. (C) 1997 Academic Press Limited.