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Coupling intercellular adhesion and cell polarity signaling at epidermal junctions

Co-workers: Martim Dias Gomes, Michael Saynisch

The skin is a tensile tissue constantly exposed to mechanical stress. How polarity proteins cooperate in stratified epithelia like the epidermis, and how such cross-talk affects chemical and mechanical signalling at epidermal adhesions is currently not known. We recently revealed essential roles of the polarity protein Par3 in skin cancer and found that junction-localized but not cytoplasmic Par3 promotes growth and survival (see Iden et al., Cancer Cell 2012). Despite low polarization of individual cells, epidermal junction formation and maturation requires balanced activities of apical vs. basolateral polarity proteins to achieve force homeostasis, though the underlying mechanisms remain unclear. We previously found that disturbed Par3 complex function results in an inside-out skin barrier defect in vivo, accompanied by altered expression and localization of tight junction components (see Ali et al., 2016). Moreover, our data showed that epidermal Par3 controls P-cadherin-mediated adhesion in the epidermis, which orchestrates crosstalk between different skin resident cell types (see Mescher, Jeong et al., JEM 2017). In this DFG-funded project we ask how junctional polarity proteins contribute to epidermal mechanosensation and -transduction upon varying extrinsic and intrinsic forces. We investigate the antagonism of different polarity complexes and its role in balancing intercellular adhesion and actomyosin contractility. Moreover, we investigate how mechanical forces in epidermal cells affect polarity protein-mediated junction-derived chemical signalling that couples intercellular adhesion to growth control. In collaboration with colleagues within the SPP1782, we aim at obtaining insight into the spatiotemporal relation of adhesion-born tension and growth signalling and the role of polarity proteins therein, using light microscopy and biophysical technologies such as atomic force microscopy, traction force microscopy and cell tension systems. Collectively, this project aims at identifying conserved and species- or tissue-specific mechanisms that couple mechanical and chemical signals at epithelial junctions.