Plakoglobin suppresses epithelial proliferation and hair growth in vivo.
Plakoglobin regulates cell adhesion by providing a modulatable connection between both classical and desmosomal cadherins and their respective cytoskeletal linker proteins. Both plakoglobin and the related protein beta-catenin are posttranscriptionally upregulated in response to Wnt-1 in cultured cells. Upregulation of beta-catenin has been implicated in potentiating hyperproliferation and tumor formation. To investigate the role of plakoglobin in these functions we expressed a full-length (PG) and an NH(2)-terminally truncated form of plakoglobin (DeltaN80PG) in mouse epidermis and hair follicles, tissues which undergo continuous and easily observed postnatal renewal and remodeling. Expression of these constructs results in stunted hair growth, a phenotype that has also been observed in transgenic mice expressing Wnt3 and Dvl2 (Millar et al. 1999). Hair follicles from PG and DeltaN80PG mice show premature termination of the growth phase (anagen) of the hair cycle, an event that is regulated in part by FGF5 (Hebert et al. 1994). The proliferative rate of the epidermal cells was reduced and apoptotic changes, which are associated with entry into the regressive phase of the hair follicle cycle (catagen), occurred earlier than usual.
Charpentier
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Departments of Cell Biology and Dermatology, New York University Medical School, New York 10016, USA.
Lavker
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RM
Acquista
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Cowin
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P
D000375:Aging; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D002461:Cell Line, Transformed; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D051180:Desmoplakins; D003896:Desmosomes / Q000502:physiology / Q000648:ultrastructure*; D000078404:Epidermal Cells; D004817:Epidermis / Q000648:ultrastructure; D004847:Epithelial Cells / Q000166:cytology* / Q000648:ultrastructure; D018859:Hair Follicle / Q000166:cytology / Q000254:growth & development* / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D017384:Sequence Deletion; D014162:Transfection; D051185:gamma Catenin
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D051185:gamma Catenin