p120-catenin mediates inflammatory responses in the skin.
Although p120-catenin regulates adherens junction (AJ) stability in cultured cells, genetic studies in lower eukaryotes have not revealed a role for this protein in vivo. Using conditional targeting in mice, we show that p120 null neonatal epidermis exhibits reduced intercellular AJ components but no overt disruption in barrier function or intercellular adhesion. As the mice age, however, they display epidermal hyperplasia and chronic inflammation, typified by hair degeneration and loss of body fat. Using skin engraftments and anti-inflammatory drugs, we show that these features are not attributable to reductions in junctional cadherins and catenins, but rather NFkB activation. Both in vivo and in vitro, p120 null epidermal cells activate nuclear NFkB, triggering a cascade of proinflammatory NFkB targets. Although the underlying mechanism is likely complex, we show that p120 affects NFkB activation and immune homeostasis in part through regulation of Rho GTPases. These findings provide important new insights into p120 function.
Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
Mirna
M
Perez-Moreno
Michael A
MA
Davis
Ellen
E
Wong
H Amalia
HA
Pasolli
Albert B
AB
Reynolds
Elaine
E
Fuchs
D022005:Adherens Junctions / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003872:Dermatitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000095002:Delta Catenin
D051177:Catenins; D015815:Cell Adhesion Molecules; D016328:NF-kappa B; D010750:Phosphoproteins; D020741:rho GTP-Binding Proteins; D000095002:Delta Catenin