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Myozenin: an alpha-actinin- and gamma-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.

SUBMITTER: Takada F

PROVIDER: S-EPMC29302 | biostudies-literature | 2001 Feb

REPOSITORIES: biostudies-literature

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Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines.

Takada F F 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

Proceedings of the National Academy of Sciences of the United States of America 20010206 4

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 ...[more]

PMID: 11171996

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Project description:Background:We sought to examine how 12 weeks of resistance exercise training (RET) affected skeletal muscle myofibrillar and sarcoplasmic protein levels along with markers of mitochondrial physiology in high versus low anabolic responders. Methods:Untrained college-aged males were classified as anabolic responders in the top 25th percentile (high-response cluster (HI); n = 13, dual x-ray absorptiometry total body muscle mass change (?) = +3.1 ± 0.3 kg, ? vastus lateralis (VL) thickness = +0.59 ± 0.05 cm, ? muscle fiber cross sectional area = +1,426 ± 253 ?m2) and bottom 25th percentile (low-response cluster (LO); n = 12, +1.1 ± 0.2 kg, +0.24 ± 0.07 cm, +5 ± 209 ?m2; p < 0.001 for all ? scores compared to HI). VL muscle prior to (PRE) and following RET (POST) was assayed for myofibrillar and sarcoplasmic protein concentrations, myosin and actin protein content, and markers of mitochondrial volume. Proteins related to myofibril formation, as well as whole lysate PGC1-? protein levels were assessed. Results:Main effects of cluster (HI > LO, p = 0.018, Cohen's d = 0.737) and time (PRE > POST, p = 0.037, Cohen's d = -0.589) were observed for citrate synthase activity, although no significant interaction existed (LO PRE = 1.35 ± 0.07 mM/min/mg protein, LO POST = 1.12 ± 0.06, HI PRE = 1.53 ± 0.11, HI POST = 1.39 ± 0.10). POST myofibrillar myozenin-1 protein levels were up-regulated in the LO cluster (LO PRE = 0.96 ± 0.13 relative expression units, LO POST = 1.25 ± 0.16, HI PRE = 1.00 ± 0.11, HI POST = 0.85 ± 0.12; within-group LO increase p = 0.025, Cohen's d = 0.691). No interactions or main effects existed for other assayed markers. Discussion:Our data suggest myofibrillar or sarcoplasmic protein concentrations do not differ between HI versus LO anabolic responders prior to or following a 12-week RET program. Greater mitochondrial volume in HI responders may have facilitated greater anabolism, and myofibril myozenin-1 protein levels may represent a biomarker that differentiates anabolic responses to RET. However, mechanistic research validating these hypotheses is needed.

Dataset Information

Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines.

Publications

Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines.

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