Potter, Beth Ann
(2006)
N-glycan-dependent apical trafficking of the sialomucin endolyn.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Crucial to the function of polarized epithelial cells is the generation and maintenance of distinct protein populations at the apical and basolateral domains. Cellular mechanisms sustain this polarity by properly sorting apical and basolateral proteins in both the biosynthetic and postendocytic pathways via sorting signals inherent within the protein. N-glycosylation has been specifically implicated as one of several sorting signals responsible for delivery of proteins to the apical surface along the biosynthetic pathway. Whether this sorting signal is also used along the postendocytic pathway is currently not known. To examine N-glycan-dependent trafficking along the biosynthetic pathway and explore a possible role for N-glycans in sorting along the postendocytic pathway, this study focuses on the sialomucin endolyn. Characterization of the biosynthetic sorting signal revealed that two glycans at amino acid positions 68 and 74 were necessary and sufficient for apical delivery of endolyn. Terminal processing of N-glycans is also necessary for efficient apical delivery as incubation with kifunensine, a drug that inhibits terminal processing of N-glycans, resulted in the nonpolarized delivery of endolyn. A similar N-glycan-dependent sorting signal was also found to be important for apical recycling of endolyn along the postendocytic pathway. The use of the same sorting signal suggested that endolyn may be sorted in a compartment that is common to both the biosynthetic and postendocytic pathway. However, further studies revealed that endolyn is sorted in distinct compartments along these two pathways. These data enhance our understanding of how and where N-glycans mediate apical sorting to maintain the integrity of polarized sorting in epithelial cells.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
9 October 2006 |
| Date Type: |
Completion |
| Defense Date: |
12 September 2006 |
| Approval Date: |
9 October 2006 |
| Submission Date: |
2 October 2006 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Molecular Virology and Microbiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
; apical sorting; biosynnthetic sorting; polarized epithelial cells; postendocytic sorting |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-10022006-135959/, etd-10022006-135959 |
| Date Deposited: |
10 Nov 2011 20:02 |
| Last Modified: |
15 Nov 2016 13:50 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/9426 |
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