The Actin-Binding Protein alpha-Adducin Modulates Desmosomal Turnover and Plasticity

Hiermaier, Matthias; Kliewe, Felix; Schinner, Camilla; Studle, Chiara; Maly, I. Piotr; Wanuske, Marie-Therese; Roetzer, Vera; Endlich, Nicole; Vielmuth, Franziska; Waschke, Jens und Spindler, Volker (2021): The Actin-Binding Protein alpha-Adducin Modulates Desmosomal Turnover and Plasticity. In: Journal of Investigative Dermatology, Bd. 141, Nr. 5: 1219-

Abstract

Intercellular adhesion is essential for tissue integrity and homeostasis. Desmosomes are abundant in the epidermis and the myocardium-tissues, which are under constantly changing mechanical stresses. Yet, it is largely unclear whether desmosomal adhesion can be rapidly adapted to changing demands, and the mechanisms underlying desmosome turnover are only partially understood. In this study we show that the loss of the actin-binding protein alpha-adducin resulted in reduced desmosome numbers and prevented the ability of cultured keratinocytes or murine epidermis to withstand mechanical stress. This effect was not primarily caused by decreased levels or impaired adhesive properties of desmosomal molecules but rather by altered desmosome turnover. Mechanistically, reduced cortical actin density in alpha-adducin knockout keratinocytes resulted in increased mobility of the desmosomal adhesion molecule desmoglein 3 and impaired interactions with E-cadherin, a crucial step in desmosome formation. Accordingly, the loss of alpha-adducin prevented increased membrane localization of desmoglein 3 in response to cyclic stretch or shear stress. Our data demonstrate the plasticity of desmosomal molecules in response to mechanical stimuli and unravel a mechanism of how the actin cytoskeleton indirectly shapes intercellular adhesion by restricting the membrane mobility of desmosomal molecules.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0022-202X
• Sprache: Englisch