Human skeletal muscle-specific alpha-actinin-2 and -3 isoforms form homodimers and heterodimers in vitro and in vivo.
Alpha-actinins belong to a family of actin-binding and crosslinking proteins and are expressed in many different cell types. Multiple isoforms of alpha-actinin are found in humans and are encoded by at least four distinct genes. Human skeletal muscle contains two sarcomeric isoforms, alpha-actinin-2 and -3. Previous studies have shown that the alpha-actinins function as anti-parallel homodimers but the question of heterodimer formation between two different isoforms expressed in the same cell type has not been explored. To address this issue, we expressed both alpha-actinin-2 and -3 in vitro and were able to detect their interaction by both blot overlay and co-immunoprecipitation methods. We were also able to demonstrate the presence of heterodimers in vivo in human skeletal muscle and in COS-1 cells transiently transfected with both isoforms. Our results clearly demonstrate the potential for alpha-actinin isoforms to form heterodimers which might have unique functional characteristics.
Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts, USA.
Y
Y
Chan
H Q
HQ
Tong
A H
AH
Beggs
L M
LM
Kunkel
D000185:Actinin / Q000737:chemistry* / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D019281:Dimerization; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000737:chemistry*; D011233:Precipitin Tests; D011487:Protein Conformation; D014162:Transfection
D000185:Actinin