title: Plakoglobin-dependent regulation of keratinocyte apoptosis by Rnd3.
abstract: The human epidermis is a self-renewing, stratified epithelial tissue that provides the protective function of the skin. The principal cell type within the epidermis is the keratinocyte, and normal function of the epidermis requires that keratinocyte proliferation, differentiation and cell death be carefully controlled. There is clear evidence that signalling through adhesion receptors such as integrins and cadherins plays a key role in regulating epidermal function. Previous work has shown that Rho family GTPases regulate cadherin- and integrin-based adhesion structures and hence epidermal function. In this study, we show that a member of this family, Rnd3, regulates desmosomal cell-cell adhesion in that loss of Rnd3 expression leads to an increase in desmosomes at sites of cell-cell adhesion and altered colony morphology. Loss of Rnd3 expression is also associated with resistance to cisplatin-mediated apoptosis in keratinocytes and this resistance is mediated through the desmosomal protein plakoglobin. We propose a novel plakoglobin-dependent role for Rnd3 in the regulation of keratinocyte cell death.
authors.affiliation: School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, UK.
authors.forename: Katie R
authors.initials: KR
authors.lastname: Ryan
authors.forename: Frances E
authors.initials: FE
authors.lastname: Lock
authors.forename: John K
authors.initials: JK
authors.lastname: Heath
authors.forename: Neil A
authors.initials: NA
authors.lastname: Hotchin
mesh_terms: D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism; D000577:Amides; D017209:Apoptosis; D002450:Cell Communication; D002460:Cell Line; D002470:Cell Survival; D002945:Cisplatin / Q000009:adverse effects; D051180:Desmoplakins / Q000235:genetics / Q000378:metabolism*; D003896:Desmosomes / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D011725:Pyridines; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D051185:gamma Catenin; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000577:Amides; D051180:Desmoplakins; C495292:JUP protein, human; D011725:Pyridines; D034741:RNA, Small Interfering; D051185:gamma Catenin; C108830:Y 27632; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; C508705:RND3 protein, human; D020741:rho GTP-Binding Proteins; D002945:Cisplatin