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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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Immunofluorescence staining of the CPβ isoforms (A and C) and corresponding DIC images (B and D) in sections of wild-type hearts. The β1 isoform localizes predominantly to the Z-lines (A). The β2 isoform localizes to intercalated discs and in a punctate pattern at cell–cell junctions (C). Bar, 5 μm.
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Figure 8: Immunofluorescence staining of the CPβ isoforms (A and C) and corresponding DIC images (B and D) in sections of wild-type hearts. The β1 isoform localizes predominantly to the Z-lines (A). The β2 isoform localizes to intercalated discs and in a punctate pattern at cell–cell junctions (C). Bar, 5 μm.

Mentions: The distribution of the CPβ1 and CPβ2 isoforms in murine heart tissue is the same as that described previously for chicken heart tissue and cultured cardiomyocytes (Schafer et al. 1994). CPβ1 is at the Z-lines of the sarcomere (Fig. 8 A). CPβ2 is at intercalated discs and in a punctate pattern (Fig. 8 C).


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

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

Immunofluorescence staining of the CPβ isoforms (A and C) and corresponding DIC images (B and D) in sections of wild-type hearts. The β1 isoform localizes predominantly to the Z-lines (A). The β2 isoform localizes to intercalated discs and in a punctate pattern at cell–cell junctions (C). Bar, 5 μm.
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Related In: Results  -  Collection

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Figure 8: Immunofluorescence staining of the CPβ isoforms (A and C) and corresponding DIC images (B and D) in sections of wild-type hearts. The β1 isoform localizes predominantly to the Z-lines (A). The β2 isoform localizes to intercalated discs and in a punctate pattern at cell–cell junctions (C). Bar, 5 μm.
Mentions: The distribution of the CPβ1 and CPβ2 isoforms in murine heart tissue is the same as that described previously for chicken heart tissue and cultured cardiomyocytes (Schafer et al. 1994). CPβ1 is at the Z-lines of the sarcomere (Fig. 8 A). CPβ2 is at intercalated discs and in a punctate pattern (Fig. 8 C).

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