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| Identifier |
000378626 |
| Title |
Μελέτη της Ν- Γλυκοζυλίωσης της πρωτεϊνης BRI2 που εμπλέκεται στις οικογενείς άνοιες τύπου Βρετανίας και τύπου Δανίας |
| Alternative Title |
Study of glycosylation of BRI2 protein which iw involved in familiar british and danish dementias |
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Author
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Σερλιδάκη, Δέσποινα
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Thesis advisor
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Ευθυμιόπουλος, Σπύρος
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Reviewer
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Κονσούλας, Χρήστος
Στεφανής, Λεωνίδας
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| Abstract |
BRI2 (Itm2b) is a type II transmembrane protein. Different mutations of this protein
are associated with two rare neurodegenerative diseases, Familial British Dementia
(FBD) and Familial Danish Dementia (FDD). Those two dementias show remarkable
neuropathological similarities with Alzheimer’s disease (AD). Like the wild type
protein, the mutated forms undergo proteolytic processing that, in case of mutant
proteins, results in the production of peptides that are amyloidogenic and
accumulate in the brains of patients. The function of BRI2 is so far unknown. Protein
sequence analysis of BRI2 revealed a possible N-glycosylation site on asparagine 170
(N170) in its extracellular domain. It is known from other studies that Nglycosylation
is important among others for proper protein folding, stability,
trafficking and targeting, processing and biological activity. In order to better
understand the biological properties of BRI2, we decided to study its N-glycosylation
and its possible role in BRI2 cell surface expression, subcellular localization and
proteolytic processing. At first, using an N-glycosylation inhibitor, we showed that
BRI2 is actually N-glycosylated. Following that, mutation of asparagine 170 to
alanine verified that N170 is the only N-glycosylation site of the protein. This mutant
BRI2 protein was used to the following experiments. We performed biotinylation and
pulse-chase experiments with 35S in cells expressing the wild type or the mutant
protein. We observed that although both BRI2 proteins reach the cell surface, non Nglycosylated
form appears at lower amount and has a slower rate of appearance at
the cell surface than the N-glycosylated form. Moreover, YFP-tagged BRI2 proteins
were used to observe under microscope that non N-glycosylated form of the protein
accumulates intracellularly and its cell surface appearance is much lower than that of
the wild type protein. Finally, examining the secreted peptide levels of the wild type
or the mutant protein indicated that there is no effect of N-glycosylation on
proteolytic processing of BRI2. Those results contribute to the study of BRI2
physiological function and properties, which is important for the elucidation of the
pathological mechanisms that lead to neurodegeneration.
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| Language |
Greek |
| Subject |
Alzheimer Disease |
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BRI2 |
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Central Nervous System Diseases |
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Familiar British dementia |
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Familiar Danish dementia |
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Glycosylation |
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Γλυκοζυλίωση |
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Κεντρικού νευρικού συστήματος νοσήματα |
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Νόσος Alzheimer |
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Οικογενής άνοια τύπου Βρετανίας |
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Οικογενής άνοια τύπου Δανίας |
| Issue date |
2011-12-15 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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| Views |
268 |
Μελέτη της Ν- Γλυκοζυλίωσης της πρωτεϊνης BRI2 που εμπλέκεται στις οικογενείς άνοιες τύπου Βρετανίας και τύπου Δανίας
