Flotillins in the regulation of desmosomal adhesion in pemphigus
Cell-cell adhesion in the epidermis is of vital importance for the function of the skin as a barrier, and aberrant adhesion can result in severe human diseases. Therefore, it is important to understand the molecular mechanisms that regulate epidermal cell adhesion. In this project, we will study the role of the members of the flotillin protein family in desmosomal adhesion. We have shown that flotillins can form complexes with desmosomal adhesion proteins and regulate their expression. Here, we will study how flotillins influence the dynamics of desmosomal adhesion and which role they do play in pemphigus pathogenesis. A special focus will be laid on cellular trafficking steps of the desmosomal adhesion proteins, as well as on signalling events induced by pemphigus autoantibodies and their dependence on flotillins.
Prof. Dr. Ritva Tikkanen
Beckert B, Panico F, Pollmann R, Eming R, Banning A, Tikkanen R .(2019) Immortalized Human hTert/KER-CT Keratinocytes a Model System for Research on Desmosomal Adhesion and Pathogenesis of Pemphigus Vulgaris. Int J Mol Sci, doi:10.3390/ijms20133113.
Kessler EA, van Stuijvenberg L, van Bavel JJA, van Bennekom J, Zwartsen A, Rivaud MA, Vink A, Efimov IA, van Tintelen JP, Remme CA, Marc A. Vos MA, Banning A, de Boer TP, Tikkanen R, van Veen TAB. (2019) Flotillins in the intercalated disc are potential modulators of cardiac excitability. J Mol Cell Cardiol, 126:86-95.
Banning A, Babuke T, Kurrle N, Meister M, Ruonala MO, Tikkanen R. (2018) Flotillins regulate focal adhesions by interacting with α-actinin and by influencing the activation of Focal Adhesion Kinase. Cells, 7, 28; doi:10.3390/cells7040028
Meister M, Baenfer S, Gärtner U, Koskimies J, Amaddii M, Jacob R, Tikkanen R. (2017) Regulation of cargo transfer between ESCRT-0 and ESCRT-I complexes by flotillin-1 during endosomal sorting of ubiquitinated cargo. Oncogenesis 6, e344; doi:10.1038/oncsis.2017.47