CALCIUM CALMODULIN-DEPENDENT REGULATION OF THE NH2-TERMINAL F-ACTIN BINDING DOMAIN OF UTROPHIN/

The cytoskeletal proteins utrophin, dystrophin and alpha-actinin are p redicted to form antiparallel dimers thus potentially bringing their N H2-terminal F-actin binding domains in close proximity to their EF-han d containing COOH-terminal domains. This arrangement would allow for c alcium-dependent regulation of F-actin binding. We tested this hypothe sis by determining the effect of the ubiquitous calcium binding protei n calmodulin on their F-actin binding capabilities. Binding of the NH2 -terminal P-actin binding domain of utrophin to F-actin was inhibited by increasing concentrations of calmodulin in a calcium-dependent mann er. The homologous P-actin binding domains from dystrophin and alpha-a ctinin mere not regulated by calmodulin in the presence or absence of calcium. These findings have implications for the structural organisat ion of utrophin dimers and also for the replacement of dystrophin by o ver-expression of utrophin in dystrophic muscle.