Publication Date
2013
Document Type
Thesis
Committee Members
Scott Baird (Committee Member), Katherine Excoffon (Advisor), Heather Hostetler (Committee Member)
Degree Name
Master of Science (MS)
Abstract
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.
Page Count
111
Department or Program
Department of Biological Sciences
Year Degree Awarded
2013
Copyright
Copyright 2013, all rights reserved. This open access ETD is published by Wright State University and OhioLINK.
