Mouse RAGE Variant 4 Is a Dominant Membrane Receptor that Does Not Shed to Generate Soluble RAGE
| العنوان: | Mouse RAGE Variant 4 Is a Dominant Membrane Receptor that Does Not Shed to Generate Soluble RAGE |
|---|---|
| المؤلفون: | Li Lin, Naftali Horwitz, Yunqian Peng, Edward G. Lakatta |
| المصدر: | PLoS ONE, Vol 11, Iss 9, p e0153657 (2016) |
| بيانات النشر: | Public Library of Science (PLoS), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Gene isoform, Multidisciplinary, Innate immune system, Endosome, Alternative splicing, lcsh:R, lcsh:Medicine, Biology, Cell biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Biochemistry, Cell surface receptor, 030220 oncology & carcinogenesis, Extracellular, lcsh:Q, Receptor, lcsh:Science, Cellular localization |
| الوصف: | The receptor for advanced glycation end products (RAGE) is a multi-ligand, immunoglobulin-like receptor that has been implicated in aging-associated diseases. Recent studies have demonstrated that both human and murine Ager genes undergo extensive alternative splicing that generates multiple putative transcripts encoding different receptor isoforms. Except for the soluble isoform (esRAGE), the majority of putative RAGE isoforms remain unstudied. Profiling of murine Ager transcripts showed that variant transcript 4 (mRAGE_v4), the second most abundant transcript in lungs and multiple other tissues, encodes a receptor that lacks nine residues located within the C2 extracellular section close to the trans-membrane domain. We therefore characterized mRAGEV4 isoreceptor in comparison with the full-length mRAGE (mRAGEFL). Although differing in only nine residues, mRAGEFL and mRAGEV4 display very different cellular behaviors. While mRAGEFL undergoes constitutive, extensive shedding in the cell to generate sRAGE, mRAGEV4 hardly sheds. In addition, we found that while mRAGEFL can localize to both the plasma membrane and the endosome, mRAGEV4 is exclusively localized to the plasma membrane. These very different cellular localization patterns suggest that, in addition to their roles in sRAGE production, mRAGEFL and mRAGEV4 may play distinct, spatiotemporal roles in signaling and innate immune responses. Compared to mice, humans do not have the v4 transcript. Although hRAGE, like mRAGEFL, also localizes to the plasma membrane and the endosome, its rate of constitutive shedding is significantly lower. These observations provide valuable information regarding RAGE biology, and serve as a reference by which to create mouse models relating to human diseases. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::71ce4afe7a4b343ae8e9ad04a641ff6b http://europepmc.org/articles/PMC5031407?pdf=render |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....71ce4afe7a4b343ae8e9ad04a641ff6b |
| قاعدة البيانات: | OpenAIRE |
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