Abstract
Junctional adhesion molecule-A (JAM-A) is a tight junction protein that has been implicated in the regulation of migration and spreading of epithelial cells, however, mechanistic studies are lacking. We investigated the effects of dimerization-defective JAM-A mutants that either lack the distal extracellular Ig loop (DL1) or the dimerization motif (6163) on 293T cell migration and spreading. While such cells express a small amount of wild-type JAM-A, overexpression of dimerization-defective JAM-A mutants inhibited cell migration toward fibronectin and decreased spreading. These changes were accompanied by decreased cellular levels of β1 integrin expression and decreased density of focal adhesions as determined by immunofluorescence. A role for β1 integrin in these JAM-A mediated effects was supported in experiments demonstrating decreased cell migration in 293T cells treated with siRNA specific to β1 integrin and rescue of cell migration by overexpression of β1 integrin in the dimerization-defective cell lines. β1 integrin mRNA levels in all of the cell lines were the same; however, further experiments determined that treatment of JAM-A dimerization-defective cells with proteosome inhibitors MG132 and lactacystin resulted in restoration of β1 integrin protein levels to that of controls. Taken together, these results indicate that dimerization of JAM-A regulates cell migration and spreading by controlling β1 integrin protein stability through prevention of β1 integrin degradation by the proteosome. Supported by NIH R01 DK61379
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
