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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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Electron micrographs of thin sections of the left ventricles of control, TG-wtβ1, TG-wtβ2, and TG-β1L262R animals. Myofibrils of controls are well-organized with periodicity along their length and lateral alignment. The myofibrils of TG-wtβ2 (lines 2 and 3) and TG-β1L262R (line 2) were poorly organized, with short or absent Z-lines. The intercalated discs of controls consist of closely opposed, transversely oriented plasma membranes. The intercalated discs of TG-wtβ1 and TG-β1L262R mice showed a loss of organization.
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Figure 6: Electron micrographs of thin sections of the left ventricles of control, TG-wtβ1, TG-wtβ2, and TG-β1L262R animals. Myofibrils of controls are well-organized with periodicity along their length and lateral alignment. The myofibrils of TG-wtβ2 (lines 2 and 3) and TG-β1L262R (line 2) were poorly organized, with short or absent Z-lines. The intercalated discs of controls consist of closely opposed, transversely oriented plasma membranes. The intercalated discs of TG-wtβ1 and TG-β1L262R mice showed a loss of organization.

Mentions: In thin section EM, the hearts from wild-type animals had myofibrils aligned laterally from Z-line to Z-line, with distinct A and I bands, and Z- and M-lines (Fig. 6). Mitochondria had an elongated shape and were between the parallel arrays of myofibrils.


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

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

Electron micrographs of thin sections of the left ventricles of control, TG-wtβ1, TG-wtβ2, and TG-β1L262R animals. Myofibrils of controls are well-organized with periodicity along their length and lateral alignment. The myofibrils of TG-wtβ2 (lines 2 and 3) and TG-β1L262R (line 2) were poorly organized, with short or absent Z-lines. The intercalated discs of controls consist of closely opposed, transversely oriented plasma membranes. The intercalated discs of TG-wtβ1 and TG-β1L262R mice showed a loss of organization.
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Related In: Results  -  Collection

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

Figure 6: Electron micrographs of thin sections of the left ventricles of control, TG-wtβ1, TG-wtβ2, and TG-β1L262R animals. Myofibrils of controls are well-organized with periodicity along their length and lateral alignment. The myofibrils of TG-wtβ2 (lines 2 and 3) and TG-β1L262R (line 2) were poorly organized, with short or absent Z-lines. The intercalated discs of controls consist of closely opposed, transversely oriented plasma membranes. The intercalated discs of TG-wtβ1 and TG-β1L262R mice showed a loss of organization.
Mentions: In thin section EM, the hearts from wild-type animals had myofibrils aligned laterally from Z-line to Z-line, with distinct A and I bands, and Z- and M-lines (Fig. 6). Mitochondria had an elongated shape and were between the parallel arrays of myofibrils.

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