Vertebrate isoforms of actin capping protein β have distinct functions in vivo

Actin capping protein (CP) binds barbed ends of actin filaments to regulate actin assembly. CP is an alpha/beta heterodimer, Vertebrates have conserved isoforms of each subunit, Muscle cells contain two beta isoforms. beta 1 is at the Z-line; beta 2 is at the intercalated disc and cell periphery in general. To investigate the functions of the isoforms, we replaced one isoform with another using expression in hearts of transgenic mice. Mice expressing beta 2 had a severe phenotype with juvenile lethality. Myofibril architecture was severely disrupted. The beta 2 did not localize to the Z-line. Therefore, beta 1 has a distinct function that includes interactions at the Z-line. Mice expressing beta 1 showed altered morphology of the intercalated disc: without the lethality or myofibril disruption of the beta 2-expressing mice. The in vivo function of CP is presumed to involve binding barbed ends of actin filaments, To test this hypothesis, we expressed a beta 1 mutant that poorly binds actin. These mice showed both myofibril disruption and intercalated disc remodeling, as predicted. Therefore, CP beta 1 and CP beta 2 each have a distinct function that cannot be provided by the other isoform. CP beta 1 attaches actin filaments to the Z-line, and CP beta 2 organizes the actin at the intercalated discs.