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doi:10.22028/D291-34662
Titel: | Boosting endoplasmic reticulum folding capacity reduces unfolded protein response activation and intracellular accumulation of human kidney anion exchanger 1 in Saccharomyces cerevisiae |
VerfasserIn: | Li, Xiaobing Cordat, Emmanuelle Schmitt, Manfred J. Becker, Björn |
Sprache: | Englisch |
Titel: | Yeast |
Bandnummer: | 38 |
Heft: | 9 |
Seiten: | 521-534 |
Verlag/Plattform: | Wiley |
Erscheinungsjahr: | 2021 |
Freie Schlagwörter: | chaperone ER stress kidney anion exchanger 1 (kAE1) plasma membrane unfolded protein response (UPR yeast model organism |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | Human kidney anion exchanger 1 (kAE1) facilitates simultaneous efflux of bicarbonate and absorption of chloride at the basolateral membrane of α-intercalated cells. In these cells, kAE1 contributes to systemic acid–base balance along with the proton pump v-H+-ATPase and the cytosolic carbonic anhydrase II. Recent electron microscopy analyses in yeast demonstrate that heterologous expression of several kAE1 variants causes a massive accumulation of the anion transporter in intracellular membrane structures. Here, we examined the origin of these kAE1 aggregations in more detail. Using various biochemical techniques and advanced light and electron microscopy, we showed that accumulation of kAE1 mainly occurs in endoplasmic reticulum (ER) membranes which eventually leads to strong unfolded protein response (UPR) activation and severe growth defect in kAE1 expressing yeast cells. Furthermore, our data indicate that UPR activation is dose dependent and uncoupled from the bicarbonate transport activity. By using truncated kAE1 variants, we identified the C-terminal region of kAE1 as crucial factor for the increased ER stress level. Finally, a redistribution of ER-localized kAE1 to the cell periphery was achieved by boosting the ER folding capacity. Our findings not only demonstrate a promising strategy for preventing intracellular kAE1 accumulation and improving kAE1 plasma membrane targeting but also highlight the versatility of yeast as model to investigate kAE1-related research questions including the analysis of structural features, protein degradation and trafficking. Furthermore, our approach might be a promising strategy for future analyses to further optimize the cell surface targeting of other disease-related PM proteins, not only in yeast but also in mammalian cells. Take Away We analysed the intracellular transport of human kAE1 to the yeast plasma membrane. We studied the effect of human kAE1 expression on yeast growth and UPR activation. We investigated the impact of different kAE1 truncation variants on UPR induction We implemented intervention strategies to improve PM targeting of kAE1. |
DOI der Erstveröffentlichung: | 10.1002/yea.3652 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-346622 hdl:20.500.11880/31729 http://dx.doi.org/10.22028/D291-34662 |
ISSN: | 1097-0061 0749-503X |
Datum des Eintrags: | 8-Sep-2021 |
Bezeichnung des in Beziehung stehenden Objekts: | Supporting Information |
In Beziehung stehendes Objekt: | https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fyea.3652&file=yea3652-sup-0001-Figure+S1.tiff https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fyea.3652&file=yea3652-sup-0002-Figure+S2.tiff https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fyea.3652&file=yea3652-sup-0003-Data+S1.docx |
Fakultät: | ZE - Zentrale Einrichtungen |
Fachrichtung: | ZE - Zentrum für Human- und Molekularbiologie (ZHMB) |
Professur: | ZE - Sonstige |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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yea.3652.pdf | 9,91 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons