Regulation of the stability and cellular localization of the Coxsackievirus and adenovirus receptor (CAR)
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Wright State University / OhioLINK
2013
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=wright1369675943 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-wright13696759432021-08-03T05:23:42Z Regulation of the stability and cellular localization of the Coxsackievirus and adenovirus receptor (CAR) Yan, Ran Biology In polarized epithelia, the seven exon isoform of the Coxsackievirus and adenovirus receptor (CAR<sup>Ex7</sup>) is a basolateral cell-cell adhesion protein that is inaccessible for viral infection. In contrast, the eight-exon CAR isoform (CAR<sup>Ex8</sup>) 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 CAR<sup>Ex7</sup> and CAR<sup>Ex8</sup> both interact with MAGI-1-PDZ3 with high affinity. CAR<sup>Ex8</sup> also interacts with MAGI-1-PDZ1. Whereas the CAR<sup>Ex7</sup>-PDZ3 interaction regulates MAGI-1 junction localization, PDZ3 suppresses CAR<sup>Ex8</sup> cell surface levels and AdV infection. Surprisingly, PDZ1 can rescue CAR<sup>Ex8</sup> from MAGI-1-mediated degradation. I also hypothesized that MAGI-1 directs CAR<sup>Ex8</sup> to the ER-associated degradation (ERAD) pathway. Inhibitor experiments demonstrated that ERAD-UPS is associated with MAGI-1-mediated CAR<sup>Ex8</sup> degradation. These novel findings provide insight into the stability and cellular regulation of CAR. 2013-05-31 English text Wright State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=wright1369675943 http://rave.ohiolink.edu/etdc/view?acc_num=wright1369675943 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biology |
| spellingShingle |
Biology Yan, Ran Regulation of the stability and cellular localization of the Coxsackievirus and adenovirus receptor (CAR) |
| author |
Yan, Ran |
| author_facet |
Yan, Ran |
| author_sort |
Yan, Ran |
| title |
Regulation of the stability and cellular localization of the Coxsackievirus and adenovirus receptor (CAR) |
| title_short |
Regulation of the stability and cellular localization of the Coxsackievirus and adenovirus receptor (CAR) |
| title_full |
Regulation of the stability and cellular localization of the Coxsackievirus and adenovirus receptor (CAR) |
| title_fullStr |
Regulation of the stability and cellular localization of the Coxsackievirus and adenovirus receptor (CAR) |
| title_full_unstemmed |
Regulation of the stability and cellular localization of the Coxsackievirus and adenovirus receptor (CAR) |
| title_sort |
regulation of the stability and cellular localization of the coxsackievirus and adenovirus receptor (car) |
| publisher |
Wright State University / OhioLINK |
| publishDate |
2013 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=wright1369675943 |
| work_keys_str_mv |
AT yanran regulationofthestabilityandcellularlocalizationofthecoxsackievirusandadenovirusreceptorcar |
| _version_ |
1719419888871669760 |