p120-catenin mediates inflammatory responses in the skin

TY - JOUR

T1 - p120-catenin mediates inflammatory responses in the skin

AU - Perez-Moreno, Mirna

AU - Davis, Michael A

AU - Wong, Ellen

AU - Pasolli, H Amalia

AU - Reynolds, Albert B

AU - Fuchs, Elaine

PY - 2006/2/10

Y1 - 2006/2/10

N2 - 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.

AB - 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.

KW - Adherens Junctions

KW - Animals

KW - Animals, Newborn

KW - Catenins

KW - Cell Adhesion Molecules

KW - Dermatitis

KW - Humans

KW - Hyperplasia

KW - Inflammation

KW - Mice

KW - Mice, Knockout

KW - Mice, Transgenic

KW - NF-kappa B

KW - Phosphoproteins

KW - Skin

KW - rho GTP-Binding Proteins

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, U.S. Gov't, Non-P.H.S.

U2 - 10.1016/j.cell.2005.11.043

DO - 10.1016/j.cell.2005.11.043

M3 - Journal article

C2 - 16469707

SN - 0092-8674

VL - 124

SP - 631

EP - 644

JO - Cell

JF - Cell

IS - 3

ER -