Capping protein nucleates the assembly of actin filaments and stabilizes actin filaments by binding to their barbed ends. We describe here a novel isoform of the beta subunit of chicken capping protein, the beta 2 isoform, which arises by alternative splicing. The chicken beta 1 isoform and the beta 2 isoform are identical in their amino acid sequence except for a short region at the COOH terminus; this region of the beta subunit has been implicated in binding actin. Human and mouse cDNAs of the beta 1 and beta 2 isoforms also were isolated and among these vertebrates, the COOH-terminal region of each isoform is highly conserved. In contrast, comparison of the sequences of the vertebrate beta subunit COOH-termini to those of lower eukaryotes shows no similarities. The beta 2 isoform is the predominant isoform of nonmuscle tissues and the beta 1 isoform, which was first characterized in studies of capping protein from chicken muscle, is the predominant isoform of muscle tissues, as shown by immunoblots probed with isoform-specific antibodies and by RNAse protection analysis of mRNAs. The beta 2 isoform also is a component of dynactin complex from brain, which contains the actin-related protein Arp1. Both beta-subunit isoforms are expressed in cardiac muscle but they have non-overlapping subcellular distributions. The beta 1 isoform is at Z-discs of myofibrils, and the beta 2 isoform is enriched at intercalated discs; in cardiac myocytes grown in culture, the beta 2 isoform also is a component of cell-cell junctions and at sites where myofibrils contact the sarcolemma. The biochemical basis for the differential distribution of capping protein isoforms is likely due to interaction with specific proteins at Z-discs and cell-cell junctions, or to preferential association with different actin isoforms. Thus, vertebrates have developed isoforms of capping protein that associate with distinct actin-filament arrays.

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