Apical integrins as a switchable target to regulate the epithelial barrier
Issued Date
2024-12-01
Resource Type
ISSN
00219533
eISSN
14779137
Scopus ID
2-s2.0-85212775111
Pubmed ID
39552289
Journal Title
Journal of Cell Science
Volume
137
Issue
24
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Cell Science Vol.137 No.24 (2024)
Suggested Citation
Peterson R.J., Reed R.C., Zamecnik C.R., Sallam M.A., Finbloom J.A., Martinez F.J., Levy J.M., Moonwiriyakit A., Desai T.A., Koval M. Apical integrins as a switchable target to regulate the epithelial barrier. Journal of Cell Science Vol.137 No.24 (2024). doi:10.1242/jcs.263580 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/102545
Title
Apical integrins as a switchable target to regulate the epithelial barrier
Corresponding Author(s)
Other Contributor(s)
Abstract
Tight junctions regulate epithelial barrier function and have been shown to be influenced by multiple classes of proteins. Apical integrins have been identified as potential regulators of epithelial barrier function; however, only indirect approaches have been used to measure integrin regulation of the epithelial barrier. Here, we used polymeric nanowires conjugated with anti-integrin β1 antibodies to specifically target apically localized integrins in either their closed or open conformation. Barrier regulation by apical integrins was found to be conformation specific. Nanowires targeting integrins in the closed conformation increased epithelial permeability and caused zonula occludens-1 (ZO-1, also known as TJP1) to change from a linear to a ruffled morphology. Claudin-2 and claudin-4 colocalized with ZO-1 and were also ruffled; however, claudin-1 and claudin-7 remained linear. Ruffling was dependent on myosin light chain kinases (MLCKs) and Rho kinases (ROCKs). Conversely, targeting integrins in the open conformation decreased epithelial permeability and made junctions more linearized. Anti-integrin β1 nanowires differentially affected actin and talin (analyzed using pan-talin antibodies), depending on whether they contained activating or inhibitory antibodies. Thus, apical integrins can act as a conformation-sensitive switch that regulates epithelial barrier function.