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Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation.

Grossmann KS, Grund C, Huelsken J, Behrend M, Erdmann B, Franke WW, Birchmeier W - J. Cell Biol. (2004)

Bottom Line: Plakophilins are proteins of the armadillo family that function in embryonic development and in the adult, and when mutated can cause disease.By contrast, embryonic epithelia show normal junctions.Thus, we conclude that plakophilin 2 is important for the assembly of junctional proteins and represents an essential morphogenic factor and architectural component of the heart.

View Article: PubMed Central - PubMed

Affiliation: Max Delbrueck Center for Molecular Medicine (MDC), D-13092 Berlin, Germany.

ABSTRACT
Plakophilins are proteins of the armadillo family that function in embryonic development and in the adult, and when mutated can cause disease. We have ablated the plakophilin 2 gene in mice. The resulting mutant mice exhibit lethal alterations in heart morphogenesis and stability at mid-gestation (E10.5-E11), characterized by reduced trabeculation, disarrayed cytoskeleton, ruptures of cardiac walls, and blood leakage into the pericardiac cavity. In the absence of plakophilin 2, the cytoskeletal linker protein desmoplakin dissociates from the plaques of the adhering junctions that connect the cardiomyocytes and forms granular aggregates in the cytoplasm. By contrast, embryonic epithelia show normal junctions. Thus, we conclude that plakophilin 2 is important for the assembly of junctional proteins and represents an essential morphogenic factor and architectural component of the heart.

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IFs around a granular desmoplakin aggregate in a cardiomyocyte of a plakophilin 2–deficient E10.75 mouse embryo. Immunoelectron micrograph of an ultrathin section, showing a typical dense granular aggregate (arrow) containing desmoplakin surrounded by extended swirls of nonordered, loosely arranged IFs. Note the occurrence of desmoplakin gold label in the aggregate, as well as being distributed in a dispersed state over the entire IF swirl. Bar, 0.5 μm.
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fig6: IFs around a granular desmoplakin aggregate in a cardiomyocyte of a plakophilin 2–deficient E10.75 mouse embryo. Immunoelectron micrograph of an ultrathin section, showing a typical dense granular aggregate (arrow) containing desmoplakin surrounded by extended swirls of nonordered, loosely arranged IFs. Note the occurrence of desmoplakin gold label in the aggregate, as well as being distributed in a dispersed state over the entire IF swirl. Bar, 0.5 μm.

Mentions: By contrast, in the hearts of the plakophilin 2–deficient embryos the location of desmoplakin was drastically altered: immunogold labeling demonstrated that desmoplakin was virtually absent from all junctions (Fig. 5, d and f). Instead, desmoplakin immunolabel was found in sparse distribution over the cytoplasm and often appeared at dense granular aggregates of diameters of up to 1 μm, mostly located deep between the bundles of myofibrils or in association with the tangles of IFs (Fig. 5, i and j), which were positive for desmin and for vimentin (unpublished data). However, the distribution of N-cadherin and other plaque components examined (e.g., α- and β-catenin) was not significantly altered in the hearts of the wt and the plakophilin 2–deficient embryos (Fig. 5, k and l; unpublished data). In many places, IF arrays appeared locally displaced by the aggregates of desmoplakin granules (Fig. 5, i and j). The extent of changes of cytoskeletal organization in the absence of plakophilin 2 is presented at higher magnification in Fig. 6: we frequently observed conspicuous IF arrays, which appeared as extensive swirls of disordered filaments around the dense desmoplakin aggregates (Fig. 6, arrow). In addition, some desmoplakin immunolabel was always identified in association with the extensive IF tangles (Fig. 6).


Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation.

Grossmann KS, Grund C, Huelsken J, Behrend M, Erdmann B, Franke WW, Birchmeier W - J. Cell Biol. (2004)

IFs around a granular desmoplakin aggregate in a cardiomyocyte of a plakophilin 2–deficient E10.75 mouse embryo. Immunoelectron micrograph of an ultrathin section, showing a typical dense granular aggregate (arrow) containing desmoplakin surrounded by extended swirls of nonordered, loosely arranged IFs. Note the occurrence of desmoplakin gold label in the aggregate, as well as being distributed in a dispersed state over the entire IF swirl. Bar, 0.5 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172504&req=5

fig6: IFs around a granular desmoplakin aggregate in a cardiomyocyte of a plakophilin 2–deficient E10.75 mouse embryo. Immunoelectron micrograph of an ultrathin section, showing a typical dense granular aggregate (arrow) containing desmoplakin surrounded by extended swirls of nonordered, loosely arranged IFs. Note the occurrence of desmoplakin gold label in the aggregate, as well as being distributed in a dispersed state over the entire IF swirl. Bar, 0.5 μm.
Mentions: By contrast, in the hearts of the plakophilin 2–deficient embryos the location of desmoplakin was drastically altered: immunogold labeling demonstrated that desmoplakin was virtually absent from all junctions (Fig. 5, d and f). Instead, desmoplakin immunolabel was found in sparse distribution over the cytoplasm and often appeared at dense granular aggregates of diameters of up to 1 μm, mostly located deep between the bundles of myofibrils or in association with the tangles of IFs (Fig. 5, i and j), which were positive for desmin and for vimentin (unpublished data). However, the distribution of N-cadherin and other plaque components examined (e.g., α- and β-catenin) was not significantly altered in the hearts of the wt and the plakophilin 2–deficient embryos (Fig. 5, k and l; unpublished data). In many places, IF arrays appeared locally displaced by the aggregates of desmoplakin granules (Fig. 5, i and j). The extent of changes of cytoskeletal organization in the absence of plakophilin 2 is presented at higher magnification in Fig. 6: we frequently observed conspicuous IF arrays, which appeared as extensive swirls of disordered filaments around the dense desmoplakin aggregates (Fig. 6, arrow). In addition, some desmoplakin immunolabel was always identified in association with the extensive IF tangles (Fig. 6).

Bottom Line: Plakophilins are proteins of the armadillo family that function in embryonic development and in the adult, and when mutated can cause disease.By contrast, embryonic epithelia show normal junctions.Thus, we conclude that plakophilin 2 is important for the assembly of junctional proteins and represents an essential morphogenic factor and architectural component of the heart.

View Article: PubMed Central - PubMed

Affiliation: Max Delbrueck Center for Molecular Medicine (MDC), D-13092 Berlin, Germany.

ABSTRACT
Plakophilins are proteins of the armadillo family that function in embryonic development and in the adult, and when mutated can cause disease. We have ablated the plakophilin 2 gene in mice. The resulting mutant mice exhibit lethal alterations in heart morphogenesis and stability at mid-gestation (E10.5-E11), characterized by reduced trabeculation, disarrayed cytoskeleton, ruptures of cardiac walls, and blood leakage into the pericardiac cavity. In the absence of plakophilin 2, the cytoskeletal linker protein desmoplakin dissociates from the plaques of the adhering junctions that connect the cardiomyocytes and forms granular aggregates in the cytoplasm. By contrast, embryonic epithelia show normal junctions. Thus, we conclude that plakophilin 2 is important for the assembly of junctional proteins and represents an essential morphogenic factor and architectural component of the heart.

Show MeSH
Related in: MedlinePlus