alpha-actinin-2 is a new component of the dystrophin-glycoprotein complex.
The human skeletal muscle yeast two-hybrid cDNA library was screened with the carboxyl-terminal region (the last 200 amino acids) of dystrophin. Two interacting clones were identified corresponding to alpha-actinin-2 and actin. Interactions between alpha-actinin, actin, and dystrophin were confirmed by the ligand-blotting technique, by colocalization of dystrophin and alpha-actinin-2 to the isolated skeletal muscle sarcolemmal vesicles and to the plasma membranes isolated from C2C12 myoblasts, and by indirect immunolocalization of dystrophin and alpha-actinin-2 in skeletal muscle cells. This is the first identification of a direct interaction between alpha-actinin, actin, and the carboxyl-terminal region of dystrophin. We propose that dystrophin forms lateral, multicontact association with actin and that binding of alpha-actinin-2 to the carboxyl-terminus of dystrophin is the communication link between the integrins and the dystrophin/dystrophin-glycoprotein complex.
D000185:Actinin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D000199:Actins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D016189:Dystrophin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D015723:Gene Library; D006023:Glycoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D012508:Sarcolemma / Q000737:chemistry / Q000378:metabolism