Desmosomal Hyperadhesion Is Accompanied with Enhanced Binding Strength of Desmoglein 3 Molecules

• Published in: Biophysical journal Vol. 119; no. 8; pp. 1489 - 1500
• Main Authors: Fuchs, Michael, Sigmund, Anna Magdalena, Waschke, Jens, Vielmuth, Franziska
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.10.2020; The Biophysical Society
• Subjects: Animals; Cell Adhesion; Desmoglein 3; Humans; Keratinocytes; Mice; Microscopy, Atomic Force; Plakophilins; Skin
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/j.bpj.2020.09.008

Intercellular adhesion of keratinocytes depends critically on desmosomes that, during maturation, acquire a hyperadhesive and thus Ca2+ independent state. Here, we investigated the roles of desmoglein (Dsg) 3 and plakophilins (Pkps) in hyperadhesion. Atomic force microscopy single molecule force mappings revealed increased Dsg3 molecules but not Dsg1 molecules binding strength in murine keratinocytes. However, keratinocytes lacking Dsg3 or Pkp1 or 3 revealed reduced Ca2+ independency. In addition, Pkp1- or 3-deficient keratinocytes did not exhibit changes in Dsg3 binding on the molecular level. Further, wild-type keratinocytes showed increased levels of Dsg3 oligomers during acquisition of hyperadhesion, and Pkp1 deficiency abolished the formation of Ca2+ independent Dsg3 oligomers. In concordance, immunostaining for Dsg1 but not for Dsg3 was reduced after 24 h of Ca2+ chelation in an ex vivo human skin model, suggesting that desmosomal cadherins may have different roles during acquisition of hyperadhesion. Taken together, these data indicate that hyperadhesion may not be a state acquired by entire desmosomes but rather is paralleled by enhanced binding of specific Dsg isoforms such as Dsg3, a process for which plaque proteins including Pkp 1 and 3 are required as well.