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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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Electron micrographs showing near-normal morphology of adhering junctions in epithelial tissues at E10.75 of wt and plakophilin 2–deficient embryos. (a and b) In the periderm of the developing epidermis of both wt (a) and pkp2−/− (b) embryos, desmosomes with similar ultrastructure are seen, often adjacent to small adherens junctions (e.g., to the left of the desmosome in b). (c, wt; d and e, pkp2−/−) Similarly, both desmosomes and adherens junctions are seen side by side in other forming epithelia such as in the stomach mucosa. The higher magnification picture (e) reveals normal plaque thickness and density, trilaminar membrane appearance, and bridge structures in the intermembranous desmoglea structure. Bars: 0.1 μm (a, b, and e) and 0.5 μm (c and d).
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fig7: Electron micrographs showing near-normal morphology of adhering junctions in epithelial tissues at E10.75 of wt and plakophilin 2–deficient embryos. (a and b) In the periderm of the developing epidermis of both wt (a) and pkp2−/− (b) embryos, desmosomes with similar ultrastructure are seen, often adjacent to small adherens junctions (e.g., to the left of the desmosome in b). (c, wt; d and e, pkp2−/−) Similarly, both desmosomes and adherens junctions are seen side by side in other forming epithelia such as in the stomach mucosa. The higher magnification picture (e) reveals normal plaque thickness and density, trilaminar membrane appearance, and bridge structures in the intermembranous desmoglea structure. Bars: 0.1 μm (a, b, and e) and 0.5 μm (c and d).

Mentions: Remarkably, the ultrastructure of adherens junctions and desmosomes in epithelial tissues, such as in the forming epidermis and in stomach mucosa, was not altered in the plakophilin 2–deficient mutant mice (Fig. 7). Similarly, no significant morphological changes were noted in the aorta as well as in endothelia of blood vessels (unpublished data).


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)

Electron micrographs showing near-normal morphology of adhering junctions in epithelial tissues at E10.75 of wt and plakophilin 2–deficient embryos. (a and b) In the periderm of the developing epidermis of both wt (a) and pkp2−/− (b) embryos, desmosomes with similar ultrastructure are seen, often adjacent to small adherens junctions (e.g., to the left of the desmosome in b). (c, wt; d and e, pkp2−/−) Similarly, both desmosomes and adherens junctions are seen side by side in other forming epithelia such as in the stomach mucosa. The higher magnification picture (e) reveals normal plaque thickness and density, trilaminar membrane appearance, and bridge structures in the intermembranous desmoglea structure. Bars: 0.1 μm (a, b, and e) and 0.5 μm (c and d).
© Copyright Policy
Related In: Results  -  Collection

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

fig7: Electron micrographs showing near-normal morphology of adhering junctions in epithelial tissues at E10.75 of wt and plakophilin 2–deficient embryos. (a and b) In the periderm of the developing epidermis of both wt (a) and pkp2−/− (b) embryos, desmosomes with similar ultrastructure are seen, often adjacent to small adherens junctions (e.g., to the left of the desmosome in b). (c, wt; d and e, pkp2−/−) Similarly, both desmosomes and adherens junctions are seen side by side in other forming epithelia such as in the stomach mucosa. The higher magnification picture (e) reveals normal plaque thickness and density, trilaminar membrane appearance, and bridge structures in the intermembranous desmoglea structure. Bars: 0.1 μm (a, b, and e) and 0.5 μm (c and d).
Mentions: Remarkably, the ultrastructure of adherens junctions and desmosomes in epithelial tissues, such as in the forming epidermis and in stomach mucosa, was not altered in the plakophilin 2–deficient mutant mice (Fig. 7). Similarly, no significant morphological changes were noted in the aorta as well as in endothelia of blood vessels (unpublished data).

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