α-Actinin-2 Is a New Component of the Dystrophin–Glycoprotein Complex

• Published in: Archives of biochemistry and biophysics Vol. 365; no. 2; pp. 216 - 222
• Main Authors: Hance, Jacqueline E., Fu, Susan Y., Watkins, Simon C., Beggs, Alan H., Michalak, Marek
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.05.1999
• Subjects: actin; actinin; Actinin - chemistry; Actinin - isolation & purification; Actinin - metabolism; Actins - chemistry; Actins - isolation & purification; Actins - metabolism; Cell Line; Cloning, Molecular; Duchenne muscular dystrophy; dystrophin; Dystrophin - chemistry; Dystrophin - isolation & purification; Dystrophin - metabolism; Gene Library; Glycoproteins - chemistry; Glycoproteins - isolation & purification; Glycoproteins - metabolism; Humans; Male; Models, Molecular; Muscle, Skeletal - metabolism; Protein Conformation; Recombinant Proteins - chemistry; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; Sarcolemma - chemistry; Sarcolemma - metabolism; actin; dystrophin; actinin; Duchenne muscular dystrophy
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1006/abbi.1999.1172

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 α-actinin-2 and actin. Interactions between α-actinin, actin, and dystrophin were confirmed by the ligand-blotting technique, by colocalization of dystrophin and α-actinin-2 to the isolated skeletal muscle sarcolemmal vesicles and to the plasma membranes isolated from C2C12myoblasts, and by indirect immunolocalization of dystrophin and α-actinin-2 in skeletal muscle cells. This is the first identification of a direct interaction between α-actinin, actin, and the carboxyl-terminal region of dystrophin. We propose that dystrophin forms lateral, multicontact association with actin and that binding of α-actinin-2 to the carboxyl-terminus of dystrophin is the communication link between the integrins and the dystrophin/dystrophin–glycoprotein complex.