دورية أكاديمية
XPR1: a regulator of cellular phosphate homeostasis rather than a Pi exporter.
| العنوان: | XPR1: a regulator of cellular phosphate homeostasis rather than a Pi exporter. |
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| المؤلفون: | Burns D; Biosciences Institute, Newcastle University, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK., Berlinguer-Palmini R; Bio-Imaging Unit, The Medical School, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK., Werner A; Biosciences Institute, Newcastle University, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK. andreas.werner@ncl.ac.uk. |
| المصدر: | Pflugers Archiv : European journal of physiology [Pflugers Arch] 2024 May; Vol. 476 (5), pp. 861-869. Date of Electronic Publication: 2024 Mar 20. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Country of Publication: Germany NLM ID: 0154720 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-2013 (Electronic) Linking ISSN: 00316768 NLM ISO Abbreviation: Pflugers Arch Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Berlin, New York, Springer. |
| مواضيع طبية MeSH: | Homeostasis*/physiology , Phosphates*/metabolism, Animals ; Humans ; Cell Membrane/metabolism ; Oocytes/metabolism ; Xenopus laevis ; Xenotropic and Polytropic Retrovirus Receptor |
| مستخلص: | Phosphate (Pi) is an essential nutrient, and its plasma levels are under tight hormonal control. Uphill transport of Pi into cells is mediated by the two Na-dependent Pi transporter families SLC34 and SLC20. The molecular identity of a potential Pi export pathway is controversial, though XPR1 has recently been suggested by Giovannini and coworkers to mediate Pi export. We expressed XPR1 in Xenopus oocytes to determine its functional characteristics. Xenopus isoforms of proteins were used to avoid species incompatibility. Protein tagging confirmed the localization of XPR1 at the plasma membrane. Efflux experiments, however, failed to detect translocation of Pi attributable to XPR1. We tested various counter ions and export medium compositions (pH, plasma) as well as potential protein co-factors that could stimulate the activity of XPR1, though without success. Expression of truncated XPR1 constructs and individual domains of XPR1 (SPX, transmembrane core, C-terminus) demonstrated downregulation of the uptake of Pi mediated by the C-terminal domain of XPR1. Tethering the C-terminus to the transmembrane core changed the kinetics of the inhibition and the presence of the SPX domain blunted the inhibitory effect. Our observations suggest a regulatory role of XPR1 in cellular Pi handling rather than a function as Pi exporter. Accordingly, XPR1 senses intracellular Pi levels via its SPX domain and downregulates cellular Pi uptake via the C-terminal domain. The molecular identity of a potential Pi export protein remains therefore elusive. (© 2024. The Author(s).) |
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| معلومات مُعتمدة: | 18.011 Northern Counties Kidney Research Fund; NU-005589 Newcastle upon Tyne Hospitals NHS Charity |
| فهرسة مساهمة: | Keywords: Xenopus oocytes; Cellular phosphate balance; Phosphate exporter; XPR1 |
| المشرفين على المادة: | 0 (Phosphates) 0 (Xenotropic and Polytropic Retrovirus Receptor) |
| تواريخ الأحداث: | Date Created: 20240320 Date Completed: 20240423 Latest Revision: 20240510 |
| رمز التحديث: | 20240510 |
| مُعرف محوري في PubMed: | PMC11033234 |
| DOI: | 10.1007/s00424-024-02941-0 |
| PMID: | 38507112 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1432-2013 |
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| DOI: | 10.1007/s00424-024-02941-0 |