Myozenin: An α-actinin- and γ-filamin-binding protein of skeletal muscle Z lines

Abstract

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.

Differential Binding of Cross-Reactive Anti-DNA Antibodies to Mesangial Cells: The Role of α-Actinin

“…Although we considered the possibility that MRL/lpr and BALB/c ␣-actinin have subtle changes in binding affinity to anti-␣-actinin Abs, we believe that this is unlikely as no binding alteration was found in either of the two methods (ELISA and Western blot) that were used. ␣-Actinin 1 and 4 display some differences in cellular localization (␣-actinin 1 is concentrated in focal adhesion plaques and adherens junctions, while ␣-actinin 4 is not) and sensitivity to calcium (16,41). It remains to be seen whether the sequence polymorphisms we demonstrated here between BALB/c and MRL/lpr ACTN4 and between ACTN1 and ACTN1A will translate into measurable differences in their biochemical function and/or immunogenicity.…”

Tracking changes in Z‐band organization during myofibrillogenesis with FRET imaging

“…These proteins and their purported interactions were identified through genetic screens of muscle cDNA libraries along with yeast 2-hybrid screenings, GST pulldown and immunoprecipitation assays [Faulkner et al, 2000;Takada et al, 2001;Salmikangas et al, 2003]. Other than their primary structures, little else is known about how these proteins arrange themselves during the course of muscle development.…”

Small Leucine Zipper Protein (sLZIP) Negatively Regulates Skeletal Muscle Differentiation via Interaction with α-Actinin-4

“…There are four unique types of ACTN genes (ACTN1, 2, 3, and 4) that encode for highly homologous proteins. ACTN2 and 3 are enriched in muscle cells, whereas ACTN1 and 4 are widely expressed in other cells (5,6). In nonmuscle cells, ACTN1 and 4, which belong to the cytoskeletal isoforms, are found in actin filament bundles and adherent junctions and are involved in cell shape and motility (5,6).…”

“…ACTN2 and 3 are enriched in muscle cells, whereas ACTN1 and 4 are widely expressed in other cells (5,6). In nonmuscle cells, ACTN1 and 4, which belong to the cytoskeletal isoforms, are found in actin filament bundles and adherent junctions and are involved in cell shape and motility (5,6). ACTN2 and 3, which belong to skeletal, cardiac, and smooth muscle isoforms, are localized in the Z-disc and help in binding to actin filaments (7,8).…”