Protein exchange is reduced in calcium-independent epithelial junctions

• Published in: The Journal of cell biology Vol. 219; no. 6; p. 1
• Main Authors: Bartle, Emily I, Rao, Tejeshwar C, Beggs, Reena R, Dean, William F, Urner, Tara M, Kowalczyk, Andrew P, Mattheyses, Alexa L
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 01.06.2020
• Subjects: Adhesion; Adhesive strength; Adhesives; Biophysics; Cadherins; Cadherins - genetics; Cadherins - metabolism; Calcium; Calcium - metabolism; Calcium - pharmacology; Carbazoles - pharmacology; Catenin; Cell Adhesion - drug effects; Cell Adhesion - genetics; Cell junctions; Cell Line; Desmoglein 3 - genetics; Desmoglein 3 - metabolism; Desmoplakins - genetics; Desmoplakins - metabolism; Desmosomes; Desmosomes - drug effects; Desmosomes - metabolism; Desmosomes - ultrastructure; Exchanging; Fluorescence; Fluorescence polarization; Fluorescence recovery after photobleaching; gamma Catenin - genetics; gamma Catenin - metabolism; Humans; Keratin; Keratinocytes - drug effects; Keratinocytes - metabolism; Microscopy, Electron; Microscopy, Fluorescence; Mutation; Phosphorylation; Plastic properties; Plasticity; Protein Binding - genetics; Protein kinase C; Protein Kinase C-alpha - antagonists & inhibitors; Protein Kinase Inhibitors - pharmacology; Proteins
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201906153

Desmosomes are cell-cell junctions that provide mechanical integrity to epithelial and cardiac tissues. Desmosomes have two distinct adhesive states, calcium-dependent and hyperadhesive, which balance tissue plasticity and strength. A highly ordered array of cadherins in the adhesive interface is hypothesized to drive hyperadhesion, but how desmosome structure confers adhesive state is still elusive. We employed fluorescence polarization microscopy to show that cadherin order is not required for hyperadhesion induced by pharmacologic and genetic approaches. FRAP experiments in cells treated with the PKCα inhibitor Gö6976 revealed that cadherins, plakoglobin, and desmoplakin have significantly reduced exchange in and out of hyperadhesive desmosomes. To test whether this was a result of enhanced keratin association, we used the desmoplakin mutant S2849G, which conferred reduced protein exchange. We propose that inside-out regulation of protein exchange modulates adhesive function, whereby proteins are "locked in" to hyperadhesive desmosomes while protein exchange confers plasticity on calcium-dependent desmosomes, thereby providing rapid control of adhesion.