Characterization of human muscle type cofilin (CFL2) in normal and regenerating muscle

Cofilins are actin binding proteins and regulate actin assembly in vivo. Nu merous cofilin homologues have been characterized in various organisms incl uding mammals. In mice, a ubiquitously expressed cofilin (CFL1) and a skele tal muscle specific cofilin (CFL2) have been described. In the present stud y, we identified and characterized a human CFL2 gene localized on chromosom e 14, with high homology to murine CFL2. Furthermore, we provide evidence f or differentially spliced CFL2 transcripts (CFL2a and CFL2b). CFL2b is expr essed predominantly in human skeletal muscle and heart, while CFL2a is expr essed in various tissues. Genetic defects of CFL2 were excluded for one hum an muscle disorder, the chromosome 14 linked distal myopathy MPD1, and show n to be only possible to be a rare cause of another, nemaline myopathy. In a mouse model of mechanically induced muscle damage the changes of cofilin expression were monitored during the first 10 days of regeneration, with de phosphorylated CFL2 being the major isoform at later stages of muscle regen eration. A similar predominance of dephosphorylated CFL2 was observed in ch ronically regenerating dystrophin-deficient muscles of Duchenne muscular dy strophy patients. Therefore, the CFL2 isoform may play an important role in normal muscle function and muscle regeneration.