Protein exchange is reduced in calcium-independent epithelial junctions

• Type of Material: Article
• Authors: Emily I. Bartle, University of Alabama Birmingham; Tejeshwar C. Rao, University of Alabama Birmingham; Reena R. Beggs, University of Alabama Birmingham; William F. Dean, University of Alabama Birmingham; Tara M. Urner, University of Alabama Birmingham; Andrew Kowalczyk, Emory University; Alexa L. Mattheyses, University of Alabama Birmingham
• Language: English
• Date: 2020-06-01
• Publisher: ROCKEFELLER UNIV PRESS
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Bartle et al.
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1083/jcb.201906153
• Title of Journal or Parent Work: JOURNAL OF CELL BIOLOGY
• Volume: 219
• Issue: 6
• Grant/Funding Information: This work was supported by funding to A.L. Mattheyses from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR072697) and the National Science Foundation Career award (1832100).
• Keywords: DESMOSOMAL CADHERINS; MOLECULAR ARCHITECTURE; PKC-ALPHA; DESMOPLAKIN; Cell Biology; NANOSCALE ARCHITECTURE; HYPER-ADHESION; NUCLEAR-PORE; CELL-ADHESION; STRUCTURAL BASIS; Life Sciences & Biomedicine; Science & Technology; E-CADHERIN
• Research Categories: Engineering, Biomedical; Biology, Cell

Abstract

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.