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 sarcome ric isoforms of ol-actinin and gamma -filamin to screen a human skeletal mu scle cDNA library for interacting proteins by using the yeast two-hybrid sy stem. Here we describe myozenin (MYOZ), an alpha -actinin- and gamma -filam in-binding Z line protein expressed predominantly in skeletal muscle. Myoze nin is predicted to be a 32-kDa, globular protein with a central glycine-ri ch domain flanked by cy-helical regions with no strong homologies to any kn own genes. The MYOZ gene has six exons and maps to human chromosome 10q22.1 -q22.2, Northern blot analysis demonstrated that this transcript is express ed primarily in skeletal muscle with significantly lower levels of expressi on 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 localizatio n specifically to Z lines. Thus, myozenin is a skeletal muscle Z line prote in that may be a good candidate gene for limb-girdle muscular dystrophy or other neuromuscular disorders.