Coxsackie and Adenovirus receptor (CAR) is a member of the JAM family of adhesion receptors. CAR is located at both Mght and adherens juncMons between epithelial cells, where it assembles adhesive contacts through homodimerisaMon in trans. However, the recruitment, binding partners and signaling effects of CAR at cell juncMons and how CAR co-ordinates cell:cell and cell:matrix adhesions remain poorly understood. We have idenMfied Filamin A (FLNa), an F-acMn cross-linker, as a novel CAR-binding protein. Our biochemical analysis revealed that the cytotail of CAR phosphorylated at Ser293/Thr290 directly binds to FLNa rod1 and acMn-binding domains. FLNa is known to bind β1-integrins and negaMvely regulate integrin acMvaMon, which in turn impacts the assembly of focal adhesions. Our data demonstrates that phosphorylaMon of CAR also impacts on acMvaMon of integrins. Filamin-CAR interacMon may, thus, control the localized acMvaMon of β 1-integrins and focal adhesion assembly. Furthermore, overexpressing CAR increases epithelial cell migraMon rates and unphosphorylated CAR promotes more stable cell:cell adhesion. Taken together, our data reveals the importance of CAR as a molecular switch in controlling the cross-talk between cell:cell and cell:matrix contacts. This paves way for future studies in adhesion and migratory signaling under homeostaMc and inflammatory condiMons in epithelial cells.
CAR co-operates with Filamin A to regulate epithelial cell adhesion and migration
Raghavan, S. (Author). 2018
Student thesis: Doctoral Thesis › Doctor of Philosophy