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Litjens SHM, de Pereda JM, Sonnenberg ACurrent insights into the formation and breakdown of hemidesmosomes. Trends Cell Biol 16:376-383

Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Trends in Cell Biology (Impact Factor: 12.31). 08/2006; 16(7):376-83. DOI: 10.1016/j.tcb.2006.05.004
Source: PubMed

ABSTRACT Hemidesmosomes are multiprotein adhesion complexes that promote epithelial stromal attachment in stratified and complex epithelia. Modulation of their function is of crucial importance in a variety of biological processes, such as differentiation and migration of keratinocytes during wound healing and carcinoma invasion, in which cells become detached from the substrate and acquire a motile phenotype. Although much is known about the signaling potential of the alpha6beta4 integrin in carcinoma cells, the events that coordinate the disassembly of hemidesmosomes during differentiation and wound healing remain unclear. The binding of alpha6beta4 to plectin has a central role in hemidesmosome assembly and it is becoming clear that disrupting this interaction is a crucial event in hemidesmosome disassembly. In addition, further insight into the functional interplay between alpha3beta1 and alpha6beta4 has contributed to our understanding of hemidesmosome disassembly and cell migration.

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Available from: Arnoud Sonnenberg, Aug 31, 2015
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    • "PLAKINS IN THE EPIDERMIS Epithelial BPAG1 (BPAG1e, also called BP230) constitutes the epithelium-specific isoform of BPAG1 and is localized in basal keratinocytes in hemidesmosomes, junctional adhesion complexes that mediate dermo-epidermal cohesion (Sawamura et al., 1991; Leung et al., 2001); reviewed in (Borradori and Sonnenberg, 1999; Litjens et al., 2006). Via its N-terminal domains, BPAG1e interacts with the hemidesmosomal transmembrane proteins a6b4 integrin and BP180 (also called BPAG2 or type XVII collagen; Hopkinson and Jones, 2000; Koster et al., 2003). "
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    ABSTRACT: The plakin family consists of giant proteins involved in the cross-linking and organization of the cytoskeleton and adhesion complexes. They further modulate several fundamental biological processes, such as cell adhesion, migration, and polarization or signaling pathways. Inherited and acquired defects of plakins in humans and in animal models potentially lead to dramatic manifestations in the skin, striated muscles, and/or nervous system. These observations unequivocally demonstrate the key role of plakins in the maintenance of tissue integrity. Here we review the characteristics of the mammalian plakin members BPAG1 (bullous pemphigoid antigen 1), desmoplakin, plectin, envoplakin, epiplakin, MACF1 (microtubule-actin cross-linking factor 1), and periplakin, highlighting their role in skin homeostasis and diseases.Journal of Investigative Dermatology advance online publication, 19 December 2013; doi:10.1038/jid.2013.498.
    Journal of Investigative Dermatology 12/2013; 134(4). DOI:10.1038/jid.2013.498 · 6.37 Impact Factor
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    • "Furthermore, an a and b integrin ELISA demonstrated that the surface expression of several a and b integrins was upregulated in PKP2 KD cells (Figure 5c). We considered the possibility that the increased integrin expression had a role in the focal adhesion phenotypes described above, as it has been reported that expression of a3b1 and a6b4 negatively regulates keratinocyte migration (Litjens et al., 2006; Margadant et al., 2009). To address this possibility, control and PKP2 KD cells were silenced for either b1 or b4 integrin. "
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    ABSTRACT: Plakophilin 2 (PKP2), a desmosome component, modulates the activity and localization of the small GTPase RhoA at sites of cell-cell contact. PKP2 regulates cortical actin rearrangement during junction formation, and its loss is accompanied by an increase in actin stress fibers. We hypothesized that PKP2 may regulate focal adhesion dynamics and cell migration. Here we show that PKP2-deficient cells bind efficiently to the extracellular matrix, but upon spreading display total cell areas ∼30% smaller than control cells. Focal adhesions in PKP2-deficient cells are ∼2 × larger and more stable than in control cells, and vinculin displays an increased time for fluorescence recovery after photobleaching. Furthermore, β4 and β1 integrin protein and mRNA expression is elevated in PKP2-silenced cells. Normal focal adhesion phenotypes can be restored in PKP2-null cells by dampening the RhoA pathway or silencing β1 integrin. However, integrin expression levels are not restored by RhoA signaling inhibition. These data uncover a potential role for PKP2 upstream of β1 integrin and RhoA in integrating cell-cell and cell-substrate contact signaling in basal keratinocytes necessary for the morphogenesis, homeostasis, and reepithelialization of the stratified epidermis.Journal of Investigative Dermatology advance online publication, 25 July 2013; doi:10.1038/jid.2013.266.
    Journal of Investigative Dermatology 06/2013; 134(1). DOI:10.1038/jid.2013.266 · 6.37 Impact Factor
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    • "Studies in cultured keratinocytes have demonstrated that the association of integrin a6b4 with P1a via the integrin b4 subunit and their clustering is crucial for the formation of HDs. This initial P1a/integrin b4 association fosters the recruitment of BPAG2 and BPAG1e molecules to the complex and the anchorage of the keratin IF network through P1a and BPAG1e follows (Hopkinson and Jones 2000; Koster et al. 2003; Litjens et al. 2006). Additional stabilization of HDs against mechanical stress appears to be mediated by lateral interaction of P1a molecules via their rod domains (Walko et al. 2011). "
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    ABSTRACT: Plectin is a large, 500-kDa, intermediate filament (IF)-associated protein. It acts as a cytoskeletal crosslinker and signaling scaffold, affecting mechanical as well as dynamic properties of the cytoskeleton. As a member of the plakin family of cytolinker proteins, plectin has a multidomain structure that is responsible for its vast binding portfolio. It not only binds to all types of IFs, actin filaments and microtubules, but also to transmembrane receptors, proteins of the subplasma membrane protein skeleton, components of the nuclear envelope, and several kinases with known roles in migration, proliferation, and energy metabolism of cells. Due to alternative splicing, plectin is expressed as various isoforms with differing N-terminal heads that dictate their differential subcellular targeting. Through specific interactions with other proteins at their target sites and their ability to bind to all types of IFs, plectin molecules provide strategically located IF anchorage sites within the cytoplasm of cells. In this review, we will present an overview of the structural features and functional properties of plectin and discuss recent progress in defining the role of its isoforms in stress-prone tissues and the implicated diseases, with focus on skin, skeletal muscle, and Schwann cells of peripheral nerve.
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