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. 2024 Nov 26;13(23):1960. doi: 10.3390/cells13231960

Figure 2.

Figure 2

Model cell that visualizes the biomarkers of interest and their molecular context. In addition to the analyzed cIFs and involucrin (IVL), the following molecules were subject of the investigation: CDH1 (E-cadherin), LOR (loricrin), ITGB1 (integrin β1), ITGB3 (integrin β3), LMNB1 (lamin B1), ACTR2 (actin-related protein 2) and YAP1 (yes-associated protein). CDH1 is a constituent of adherens junctions, which connect neighboring epithelial cells to each other, thereby being indispensable for epithelial morphogenesis [48]. Intracellularly, it binds to the actin filament system via linker proteins of the catenin family [49]. In the context of epithelial keratinocyte differentiation in addition to IVL, LOR is a further marker of terminal differentiation and together with IVL participates in cornified envelope formation. LOR can form crosslinks with itself, thereby yielding different molecular weights [40]. Within the lamina-associated domains, the lamin B receptor tethers heterochromatin via LMNB1 to the inner nuclear membrane [50]. After shuttling to the nucleus, the co-transcriptional activator YAP (and its homologue TAZ, neglected in this study) binds to the TEAD family of transcription factors (TEA Domain Transcription Factor1-4), thereby inducing the expression of YAP target genes [51]. At sites of cell matrix interaction, the cIF VIM is involved in the formation of actin-bound FAs via interaction with the FAs constituent plectin [52,53]. Further constituents of FAs are ITGB1 and ITGB3, whereas ITGB3 appears to play a role in the recruitment of VIM and plectin to FAs [54]. Both of the basal cell-specific keratins, the cIFs KRT5 and KRT14, are connected with DP (Desmoplakin) [55], one of the constituents of the cytoplasmic plaque [56]. At sites of adherens junction-mediated cell-to-cell adhesion, CDH1 is linked to the actin cytoskeleton through members of the catenin family and vinculin (VCL) [57]. At sites of the nuclear envelope, ARP2/3 is involved in the formation of the actin cap, which interacts with the inner part of the nucleus through nesprin 1/2 interaction, the latter connected with the nuclear lamins nIFs via members of the Sun-family proteins Sun 1/2 (Sad1/UNC-84 domain-containing proteins) [58]. Created with BioRender.com.