Unique and redundant functions of integrins in the epidermis

Abstract

The skin forms a barrier against the environment and protects us from mechanical trauma, pathogens, radiation, dehydration, and dangerous temperature fluctuations. The epithelium of the skin, the epidermis, is in a continuous equilibrium of growth and differentiation and has the remarkable capacity to self-renew completely, which relies on reservoirs of stem cells. Epidermal homeostasis is further dependent on proper repair after injury, and on tight adhesion to the underlying basement membrane. Epidermal adhesion is mediated primarily by integrins, cell-surface receptors that connect the extracellular matrix to the cytoskeleton. In addition, numerous in vitro reports have implicated integrins, integrin-associated proteins, or downstream integrin effectors in the regulation of a plethora of cellular processes other than adhesion. Over the past decade, a wealth of information on the function of these proteins has been gathered both from (conditional) knockout mice and from human skin disorders, allowing for a reconstruction of integrin signaling pathways in vivo. Here, we address how epidermal integrins and integrin-associated proteins regulate keratinocyte adhesion, proliferation, and differentiation, as well as signal transduction, re-epithelialization during wound healing, hair growth, and stem cell maintenance. Furthermore, we discuss human pathologies associated with altered integrin functions in the epidermis.