Desmoplakin is essential in epidermal sheet formation.
We have generated an epidermis-specific desmoplakin (DP) mouse knockout, and show that epidermal integrity requires DP; mechanical stresses to DP-null skin cause intercellular separations. The number of epidermal desmosomes in DP-null skin is similar to wild type (WT), but they lack keratin filaments, which compromise their function. DP-null keratinocytes have few desmosomes in vitro, and are unable to undergo actin reorganization and membrane sealing during epithelial sheet formation. Adherens junctions are also reduced. In vitro, DP transgene expression rescues these defects. DP is therefore required for assembly of functional desmosomes, maintaining cytoskeletal architecture and reinforcing membrane attachments essential for stable intercellular adhesion.
Vasioukhin
V
V
Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois 60637, USA.
Bowers
E
E
Bauer
C
C
Degenstein
L
L
Fuchs
E
E
D022005:Adherens Junctions / Q000473:pathology / Q000648:ultrastructure; D000818:Animals; D001485:Basement Membrane / Q000737:chemistry; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D003599:Cytoskeleton / Q000737:chemistry / Q000473:pathology; D051180:Desmoplakins; D003896:Desmosomes / Q000473:pathology / Q000648:ultrastructure; D004817:Epidermis / Q000002:abnormalities* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D015603:Keratinocytes / Q000473:pathology / Q000502:physiology; D007633:Keratins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D010641:Phenotype; D013314:Stress, Mechanical
D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495295:Dsp protein, mouse; D007633:Keratins