Hemidesmosomes and focal contact proteins: Functions and cross-talk in keratinocytes, bullous diseases and wound healing

Abstract

The outer most layer of the skin, the epidermis, is attached to the dermis via a sheet of extracellular matrix proteins termed the basement membrane zone (BMZ). In the intact skin, adhesion of the keratinocytes in the basal layer of the epidermis to the BMZ is facilitated primarily by hemidesmosomes which associate with the keratin cytoskeleton. Cultured keratinocytes do not assemble bona fide hemidesmosomes although hemidesmosome protein clusters (stable anchoring contacts) are found along the substrate-attached surface of the cells and towards the leading edge of keratinocytes repopulating scratch wounds. Actin cytoskeleton-associated matrix adhesion devices termed focal contacts are not thought to play an important role in the adhesion of keratinocytes to the BMZ in intact skin but are prominent in cultured keratinocytes where they are believed to regulate cell migration. We review the molecular components, functions, dynamics and cross-talk of hemidesmosomes and focal contacts in keratinocytes. In addition, we briefly describe what is known about their role in autoimmune and genetic blistering diseases of the skin. We also discuss recent publications which indicate, contrary to expectation, that certain focal contact proteins retard keratinocyte migration while hemidesmosomal proteins regulate directed keratinocyte motility during wound healing.

Re-epithelialization of cutaneous wounds in adult zebrafish uses a combination of mechanisms at play during wound closure in embryonic and adult mammals

“…Re-epithelialization involves the dissociation of keratinocytes from the basement membrane zone at the undamaged wound margin, requiring the dissociation of hemidesmosomes and the formation of cellular protrusions pointing toward the wound. Subsequent directed migration over the wound bed requires the stimulation of focal adhesion proteins such as α5β1, α2β1, α3β1, αvβ5 and/or αvβ6 integrins, which mediate cell movement by the dynamic binding of extracellular matrix (ECM) components such as fibronectin and collagen to cell surfaces (Margadant and Sonnenberg, 2010;Tsuruta et al, 2011). Our chemical inhibitor experiments suggest that TGF-β signalling is dispensable for the protrusive activity of LE keratinocytes (Fig.…”

Plectin-containing, centrally-localized focal adhesions exert traction forces in primary lung epithelial cells

“…The presence of plectin within the inner ring of cFAs suggests that they may bear a relationship to hemidesmosomes. However, these FAs are distinct from hemidesmosomes since they contain vinculin, paxillin and talin, while hemidesmosomes do not (Litjens et al, 2006;Ozawa et al, 2010;Tsuruta et al, 2011).…”

“…First, we tracked the dynamics of GFP-paxillin by imaging cells for 20 minutes (supplementary material Fig. S4) (Ozawa et al, 2010;Tsuruta et al, 2002;Tsuruta et al, 2011). Surprisingly, we observe no dynamic movement of the cFAs, and pFAs display only limited centripetal movement (supplementary material Fig.…”

Context-Dependent Regulation of Collagen XVII Ectodomain Shedding in Skin

“…COL17 is known to be expressed not only at the DEJ but also basolaterally and in the cytoplasm 11,15 . However, the cleaved COL17 It is well characterized that migrating activated keratinocytes express distinct adhesion molecules, such as integrin α3β1 and α2β1, at the BMZ in vitro 26,27 . In addition, wound keratinocytes are known to express these distinctive integrins 28 .…”