Intercellular adhering junctions with an asymmetric molecular composition: desmosomes connecting Merkel cells and keratinocytes

Abstract

Merkel cells (MCs) are special neuroendocrine epithelial cells that occur as individual cells or as cell groups within the confinements of a major epithelium formed and dominated by other epithelial cells. In the epidermis and some of its appendages MCs are mostly located in the basal cell layer, occasionally also in suprabasal layers and generally occur in linear arrays in outer root sheath cell layers of hair follicles. As MCs are connected to the adjacent keratinocytes by a series of adhering junctions (AJs), of which the desmosomes are the most prominent, these junctions represent heterotypic cell-cell connections, i.e. a kind of structure not yet elucidated in molecular terms. Therefore, we have studied these AJs in order to examine the molecular composition of the desmosomal halves. Using light- and electron-microscopic immunolocalization and keratin 20 as the MC-specific cell type marker we show that the plaques of the MC half of the desmosomes specifically and constitutively contain plakophilin Pkp2. This protein, however, is absent in the keratinocyte half of such heterotypic desmosomes which instead contains Pkp1 and/or Pkp3. We discuss the developmental, tissue-architectonic and functional importance of such asymmetric junctions in normal physiology as well as in diseases, in particular in the formation of distant tumor cell metastasis.

Plakophilin-2: a cell-cell adhesion plaque molecule of selective and fundamental importance in cardiac functions and tumor cell growth

“…1 and 2). Remarkably, all these Pkp2 Abs also revealed the Pkp2 present in the neuroendocrine (“Merkel”) cell half of the hybrid (heterotypic) desmosomes as recently demonstrated (Rickelt et al 2011a). And, finally, the new Abs reacted rather broadly with the nuclear Pkp2 forms, showing a generally granular nucleoplasmic appearance and leaving the nucleoli negative (Figs.…”

“…Further Abs for immunofluorescence microscopy and immunoblotting analyses of gel-electrophoretically-separated polypeptides against adhering junction (AJ) proteins and glycoproteins as well as diverse cytoskeletal and nuclear proteins have been described elsewhere (e.g., Barth et al 2009; Franke and Rickelt 2011; Rickelt et al 2009, 2011a; Wuchter et al 2007). …”

“…Methods for immunofluorescence microscopy were essentially as described for cardiac tissues and cultured cardiomyocytes or interstitial cells in—or from—heart valves (Barth 2011; Barth et al 2009; Franke et al 2006; Pieperhoff and Franke 2007; Pieperhoff et al 2008, 2011; Rickelt 2010; Rickelt et al 2009, 2010, 2011a). …”

Plakophilin-3 Is Required for Late Embryonic Amphibian Development, Exhibiting Roles in Ectodermal and Neural Tissues

“…), and to gene regulation [1], [5], [8], [21], [25], [27], [59], [63], [64], [66], [67], [68]. The Pkps were first characterized in association with desmosomal junctions, which provide physical integrity to mechanically stressed tissues, such as the heart and epidermis [4], [30], [31], [37], [69], [70], [71], [72], [73]. The Pkps may further transduce extracellular signals to the nucleus.…”

The adhering junctions of valvular interstitial cells: molecular composition in fetal and adult hearts and the comings and goings of plakophilin-2 in situ, in cell culture and upon re-association with scaffolds

“…The antibodies used in this work have been listed in previous publications (Moll et al 2006;Rickelt et al 2011;Wuchter et al 2007). The specific immunoprecipitation analyses of protein complexes, followed by immunoblotting of SDS-PAGE-separated polypeptides and glycoproteins, have been described by Barth et al (2009) and Barth (2011).…”