دورية أكاديمية
Impaired phosphate transport in SLC34A2 variants in patients with pulmonary alveolar microlithiasis
| العنوان: | Impaired phosphate transport in SLC34A2 variants in patients with pulmonary alveolar microlithiasis |
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| المؤلفون: | Åsa Lina M. Jönsson, Nati Hernando, Thomas Knöpfel, Susie Mogensen, Elisabeth Bendstrup, Ole Hilberg, Jane Hvarregaard Christensen, Ulf Simonsen, Carsten A. Wagner |
| المصدر: | Human Genomics, Vol 16, Iss 1, Pp 1-11 (2022) |
| بيانات النشر: | BMC, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine LCC:Genetics |
| مصطلحات موضوعية: | Pulmonary alveolar microlithiasis (PAM), Sodium-dependent phosphate transport protein 2B, NaPi-IIb, Sodium-dependent phosphate transport protein 2B, NaPi-2b, SLC34A2, SLC34A2 variants, SLC34A2 mutations, Medicine, Genetics, QH426-470 |
| الوصف: | Abstract Background Variants in SLC34A2 encoding the sodium-dependent phosphate transport protein 2b (NaPi-IIb) cause the rare lung disease pulmonary alveolar microlithiasis (PAM). PAM is characterised by the deposition of calcium-phosphate concretions in the alveoli usually progressing over time. No effective treatment is available. So far, 30 allelic variants in patients have been reported but only a few have been functionally characterised. This study aimed to determine the impact of selected SLC34A2 variants on transporter expression and phosphate uptake in cellular studies. Methods Two nonsense variants (c.910A > T and c.1456C > T), one frameshift (c.1328delT), and one in-frame deletion (c.1402_1404delACC) previously reported in patients with PAM were selected for investigation. Wild-type and mutant c-Myc-tagged human NaPi-IIb constructs were expressed in Xenopus laevis oocytes. The transport function was investigated with a 32Pi uptake assay. NaPi-IIb protein expression and localisation were determined with immunoblotting and immunohistochemistry, respectively. Results Oocytes injected with the wild-type human NaPi-IIb construct had significant 32Pi transport compared to water-injected oocytes. In addition, the protein had a molecular weight as expected for the glycosylated form, and it was readily detectable in the oocyte membrane. Although the protein from the Thr468del construct was synthesised and expressed in the oocyte membrane, phosphate transport was similar to non-injected control oocytes. All other mutants were non-functional and not expressed in the membrane, consistent with the expected impact of the truncations caused by premature stop codons. Conclusions Of four analysed SLC34A2 variants, only the Thr468del showed similar protein expression as the wild-type cotransporter in the oocyte membrane. All mutant transporters were non-functional, supporting that dysfunction of NaPi-IIb underlies the pathology of PAM. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1479-7364 |
| العلاقة: | https://doaj.org/toc/1479-7364Test |
| DOI: | 10.1186/s40246-022-00387-y |
| الوصول الحر: | https://doaj.org/article/b26c4688d07040dca763b1684c455225Test |
| رقم الانضمام: | edsdoj.b26c4688d07040dca763b1684c455225 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14797364 |
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| DOI: | 10.1186/s40246-022-00387-y |