Inhibition of alpha-glucosidases I and II increases the cell surface expression of functional class A macrophage scavenger receptor (SR-A) by extending its half-life.
The class A scavenger receptor (SR-A) is a multifunctional trimeric membrane glycoprotein involved in atherogenesis. The mature receptor can mediate the binding and internalization of a number of specific ligands, including modified low-density lipoprotein. We have investigated the effects of inhibi...
| Κύριοι συγγραφείς: | , , , , , , |
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| Μορφή: | Journal article |
| Γλώσσα: | English |
| Έκδοση: |
2004
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| _version_ | 1826270034610094080 |
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| author | Tian, G Wilcockson, D Perry, V Rudd, P Dwek, R Platt, F Platt, N |
| author_facet | Tian, G Wilcockson, D Perry, V Rudd, P Dwek, R Platt, F Platt, N |
| author_sort | Tian, G |
| collection | OXFORD |
| description | The class A scavenger receptor (SR-A) is a multifunctional trimeric membrane glycoprotein involved in atherogenesis. The mature receptor can mediate the binding and internalization of a number of specific ligands, including modified low-density lipoprotein. We have investigated the effects of inhibiting N-glycan processing on SR-A expression, distribution, and activity in the murine macrophage cell line RAW264.7. We have found that SR-A normally interacts with calnexin in the endoplasmic reticulum and in its mature form carries complex N-glycans. The imino sugar, N-butyldeoxynojirimycin (NB-DNJ) is an inhibitor of the N-glycan processing enzymes alpha-glucosidases I and II. Following NB-DNJ treatment SR-A became Endo H-sensitive, consistent with inhibition of N-glycan processing. A dose-dependent increase in cell surface expression of SR-A was observed in response to NB-DNJ treatment. The receptor on inhibitor-treated cells was still functional because the increased surface expression resulted in a proportional enhancement in the endocytosis of the ligand, acetylated low-density lipoprotein. The expression of SR-A on NB-DNJ cultured cells was further enhanced by co-treatment with interferon-gamma. Quantitative reverse transcriptase-PCR analysis did not show a significant difference in the amount of SR-A mRNA in NB-DNJ-treated RAW264.7 cells. However, the half-life of SR-A protein was significantly increased. These data indicate the retention of glucosylated N-glycans does not result in gross misfolding and degradation of this receptor or prevent its transport to the cell surface. SR-A interacts with calnexin and when the association is prevented changes in the recycling kinetics and rate of turnover of the receptor result, leading to enhanced cell surface expression. |
| first_indexed | 2024-03-06T21:34:33Z |
| format | Journal article |
| id | oxford-uuid:45c6ffdc-3ce4-49d5-ab8f-b1d33ea5b21c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:34:33Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:45c6ffdc-3ce4-49d5-ab8f-b1d33ea5b21c2022-03-26T15:09:58ZInhibition of alpha-glucosidases I and II increases the cell surface expression of functional class A macrophage scavenger receptor (SR-A) by extending its half-life.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:45c6ffdc-3ce4-49d5-ab8f-b1d33ea5b21cEnglishSymplectic Elements at Oxford2004Tian, GWilcockson, DPerry, VRudd, PDwek, RPlatt, FPlatt, NThe class A scavenger receptor (SR-A) is a multifunctional trimeric membrane glycoprotein involved in atherogenesis. The mature receptor can mediate the binding and internalization of a number of specific ligands, including modified low-density lipoprotein. We have investigated the effects of inhibiting N-glycan processing on SR-A expression, distribution, and activity in the murine macrophage cell line RAW264.7. We have found that SR-A normally interacts with calnexin in the endoplasmic reticulum and in its mature form carries complex N-glycans. The imino sugar, N-butyldeoxynojirimycin (NB-DNJ) is an inhibitor of the N-glycan processing enzymes alpha-glucosidases I and II. Following NB-DNJ treatment SR-A became Endo H-sensitive, consistent with inhibition of N-glycan processing. A dose-dependent increase in cell surface expression of SR-A was observed in response to NB-DNJ treatment. The receptor on inhibitor-treated cells was still functional because the increased surface expression resulted in a proportional enhancement in the endocytosis of the ligand, acetylated low-density lipoprotein. The expression of SR-A on NB-DNJ cultured cells was further enhanced by co-treatment with interferon-gamma. Quantitative reverse transcriptase-PCR analysis did not show a significant difference in the amount of SR-A mRNA in NB-DNJ-treated RAW264.7 cells. However, the half-life of SR-A protein was significantly increased. These data indicate the retention of glucosylated N-glycans does not result in gross misfolding and degradation of this receptor or prevent its transport to the cell surface. SR-A interacts with calnexin and when the association is prevented changes in the recycling kinetics and rate of turnover of the receptor result, leading to enhanced cell surface expression. |
| spellingShingle | Tian, G Wilcockson, D Perry, V Rudd, P Dwek, R Platt, F Platt, N Inhibition of alpha-glucosidases I and II increases the cell surface expression of functional class A macrophage scavenger receptor (SR-A) by extending its half-life. |
| title | Inhibition of alpha-glucosidases I and II increases the cell surface expression of functional class A macrophage scavenger receptor (SR-A) by extending its half-life. |
| title_full | Inhibition of alpha-glucosidases I and II increases the cell surface expression of functional class A macrophage scavenger receptor (SR-A) by extending its half-life. |
| title_fullStr | Inhibition of alpha-glucosidases I and II increases the cell surface expression of functional class A macrophage scavenger receptor (SR-A) by extending its half-life. |
| title_full_unstemmed | Inhibition of alpha-glucosidases I and II increases the cell surface expression of functional class A macrophage scavenger receptor (SR-A) by extending its half-life. |
| title_short | Inhibition of alpha-glucosidases I and II increases the cell surface expression of functional class A macrophage scavenger receptor (SR-A) by extending its half-life. |
| title_sort | inhibition of alpha glucosidases i and ii increases the cell surface expression of functional class a macrophage scavenger receptor sr a by extending its half life |
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