Scott Baird (Committee Member), Katherine Excoffon (Advisor), Heather Hostetler (Committee Member)
Master of Science (MS)
In polarized epithelia, the seven exon isoform of the Coxsackievirus and adenovirus receptor (CAREx7) is a basolateral cell-cell adhesion protein that is inaccessible for viral infection. In contrast, the eight-exon CAR isoform (CAREx8) localizes at the apical surface and mediates adenovirus (AdV) infection. A PDZ-domain containing protein, MAGI-1, interacts with both isoforms of CAR. I hypothesized that each CAR isoform interacts with specific MAGI-1 PDZ domain(s). Co-immunoprecipitation, FRET and binding assays showed that CAREx7 and CAREx8 both interact with MAGI-1-PDZ3 with high affinity. CAREx8 also interacts with MAGI-1-PDZ1. Whereas the CAREx7-PDZ3 interaction regulates MAGI-1 junction localization, PDZ3 suppresses CAREx8 cell surface levels and AdV infection. Surprisingly, PDZ1 can rescue CAREx8 from MAGI-1-mediated degradation. I also hypothesized that MAGI-1 directs CAREx8 to the ER-associated degradation (ERAD) pathway. Inhibitor experiments demonstrated that ERAD-UPS is associated with MAGI-1-mediated CAREx8 degradation. These novel findings provide insight into the stability and cellular regulation of CAR.
Department or Program
Department of Biological Sciences
Year Degree Awarded
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