Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines.
To better understand the structure and function of Z lines, we used sarcomeric isoforms of alpha-actinin and gamma-filamin to screen a human skeletal muscle cDNA library for interacting proteins by using the yeast two-hybrid system. Here we describe myozenin (MYOZ), an alpha-actinin- and gamma-filamin-binding Z line protein expressed predominantly in skeletal muscle. Myozenin is predicted to be a 32-kDa, globular protein with a central glycine-rich domain flanked by alpha-helical regions with no strong homologies to any known genes. The MYOZ gene has six exons and maps to human chromosome 10q22.1-q22.2. Northern blot analysis demonstrated that this transcript is expressed primarily in skeletal muscle with significantly lower levels of expression in several other tissues. Antimyozenin antisera stain skeletal muscle in a sarcomeric pattern indistinguishable from that seen by using antibodies for alpha-actinin, and immunogold electron microscopy confirms localization specifically to Z lines. Thus, myozenin is a skeletal muscle Z line protein that may be a good candidate gene for limb-girdle muscular dystrophy or other neuromuscular disorders.
Takada
F
F
Division of Genetics, Children's Hospital, Boston, MA 02115, USA.
Vander Woude
D L
DL
Tong
H Q
HQ
Thompson
T G
TG
Watkins
S C
SC
Kunkel
L M
LM
Beggs
A H
AH
D000185:Actinin / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D003285:Contractile Proteins / Q000378:metabolism*; D018076:DNA, Complementary; D064448:Filamins; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*
D002352:Carrier Proteins; D003285:Contractile Proteins; D018076:DNA, Complementary; D064448:Filamins; C419780:MYOZ1 protein, human; D008840:Microfilament Proteins; D009124:Muscle Proteins; D000185:Actinin