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Vertebrate isoforms of actin capping protein beta have distinct functions In vivo.

Hart MC, Cooper JA - J. Cell Biol. (1999)

Bottom Line: The beta2 did not localize to the Z-line.Therefore, CPbeta1 and CPbeta2 each have a distinct function that cannot be provided by the other isoform.CPbeta1 attaches actin filaments to the Z-line, and CPbeta2 organizes the actin at the intercalated discs.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

ABSTRACT
Actin capping protein (CP) binds barbed ends of actin filaments to regulate actin assembly. CP is an alpha/beta heterodimer. Vertebrates have conserved isoforms of each subunit. Muscle cells contain two beta isoforms. beta1 is at the Z-line; beta2 is at the intercalated disc and cell periphery in general. To investigate the functions of the isoforms, we replaced one isoform with another using expression in hearts of transgenic mice. Mice expressing beta2 had a severe phenotype with juvenile lethality. Myofibril architecture was severely disrupted. The beta2 did not localize to the Z-line. Therefore, beta1 has a distinct function that includes interactions at the Z-line. Mice expressing beta1 showed altered morphology of the intercalated disc, without the lethality or myofibril disruption of the beta2-expressing mice. The in vivo function of CP is presumed to involve binding barbed ends of actin filaments. To test this hypothesis, we expressed a beta1 mutant that poorly binds actin. These mice showed both myofibril disruption and intercalated disc remodeling, as predicted. Therefore, CPbeta1 and CPbeta2 each have a distinct function that cannot be provided by the other isoform. CPbeta1 attaches actin filaments to the Z-line, and CPbeta2 organizes the actin at the intercalated discs.

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Progressive disorganization. Myofibrils from TG-β1L262R mice (line 2) show progressive disorganization, with milder defects at early times (A and B higher magnification) and poor myofibrillar organization by day 20 (C). Bars, (A and C) 1.1 μm; (B) 0.35 μm.
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Figure 7: Progressive disorganization. Myofibrils from TG-β1L262R mice (line 2) show progressive disorganization, with milder defects at early times (A and B higher magnification) and poor myofibrillar organization by day 20 (C). Bars, (A and C) 1.1 μm; (B) 0.35 μm.

Mentions: Abnormal cardiomyocyte structure and organization was also apparent in the left ventricles of TG-β1L262R mice, whose mutation precludes the binding of actin to CP (Fig. 6 and Fig. 7). This suggests that the myofibrillar disarray observed in the hearts of the TG-wtβ2 mice was due to the inability of CPβ2 to attach the actin filaments to the Z-line. The myofibrils of TG-β1L262R had a highly disorganized architecture, including abnormally registered sarcomeres with disoriented or missing Z-lines. The A and I bands were apparent, but lacked their typical striation. The mitochondria had lost their organization and shape.


Vertebrate isoforms of actin capping protein beta have distinct functions In vivo.

Hart MC, Cooper JA - J. Cell Biol. (1999)

Progressive disorganization. Myofibrils from TG-β1L262R mice (line 2) show progressive disorganization, with milder defects at early times (A and B higher magnification) and poor myofibrillar organization by day 20 (C). Bars, (A and C) 1.1 μm; (B) 0.35 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2168092&req=5

Figure 7: Progressive disorganization. Myofibrils from TG-β1L262R mice (line 2) show progressive disorganization, with milder defects at early times (A and B higher magnification) and poor myofibrillar organization by day 20 (C). Bars, (A and C) 1.1 μm; (B) 0.35 μm.
Mentions: Abnormal cardiomyocyte structure and organization was also apparent in the left ventricles of TG-β1L262R mice, whose mutation precludes the binding of actin to CP (Fig. 6 and Fig. 7). This suggests that the myofibrillar disarray observed in the hearts of the TG-wtβ2 mice was due to the inability of CPβ2 to attach the actin filaments to the Z-line. The myofibrils of TG-β1L262R had a highly disorganized architecture, including abnormally registered sarcomeres with disoriented or missing Z-lines. The A and I bands were apparent, but lacked their typical striation. The mitochondria had lost their organization and shape.

Bottom Line: The beta2 did not localize to the Z-line.Therefore, CPbeta1 and CPbeta2 each have a distinct function that cannot be provided by the other isoform.CPbeta1 attaches actin filaments to the Z-line, and CPbeta2 organizes the actin at the intercalated discs.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

ABSTRACT
Actin capping protein (CP) binds barbed ends of actin filaments to regulate actin assembly. CP is an alpha/beta heterodimer. Vertebrates have conserved isoforms of each subunit. Muscle cells contain two beta isoforms. beta1 is at the Z-line; beta2 is at the intercalated disc and cell periphery in general. To investigate the functions of the isoforms, we replaced one isoform with another using expression in hearts of transgenic mice. Mice expressing beta2 had a severe phenotype with juvenile lethality. Myofibril architecture was severely disrupted. The beta2 did not localize to the Z-line. Therefore, beta1 has a distinct function that includes interactions at the Z-line. Mice expressing beta1 showed altered morphology of the intercalated disc, without the lethality or myofibril disruption of the beta2-expressing mice. The in vivo function of CP is presumed to involve binding barbed ends of actin filaments. To test this hypothesis, we expressed a beta1 mutant that poorly binds actin. These mice showed both myofibril disruption and intercalated disc remodeling, as predicted. Therefore, CPbeta1 and CPbeta2 each have a distinct function that cannot be provided by the other isoform. CPbeta1 attaches actin filaments to the Z-line, and CPbeta2 organizes the actin at the intercalated discs.

Show MeSH