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 Pi 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 Pi 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019944 | PMC |
| http://dx.doi.org/10.1186/s40246-022-00387-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Optimizing Tongue Fluid Sampling and Testing Protocols for Enhanced PRRSV Isolation from Perinatal Swine Mortalities.
Viruses
January 2025
Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-3619, USA.
Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major concern for swine health. Isolating PRRSV is essential for identifying infectious viruses and for vaccine formulation. This study evaluated the potential of using tongue fluid (TF) from perinatal piglet mortalities for PRRSV isolation.
View Article and Find Full Text PDFProhexadione Calcium Improves Rice Yield Under Salt Stress by Regulating Source-Sink Relationships During the Filling Period.
Plants (Basel)
January 2025
College of Coastal Agriculture Sciences, Guangdong Ocean University, Zhanjiang 524088, China.
Salt stress is an important factor affecting the growth and development of rice, and prohexadione calcium (Pro-Ca) plays an important role in alleviating rice salt stress and improving rice yield. However, there are few studies on how Pro-Ca improves rice yield under salt stress by regulating the source-sink metabolism. In this study, we used Guanghong 3 (salt-tolerant variety) and Huanghuazhan (salt-sensitive variety) as experimental materials to investigate the dynamic changes in the synthesis and partitioning of nonstructural carbohydrates among source-sink, the dynamic changes in related enzyme activities, the effects of the source-sink metabolism on yield in rice under salt stress and the effect of Pro-Ca during the filling period.
View Article and Find Full Text PDFTwo-Step Cell Death Induction by the New 2-Arachidonoyl Glycerol Analog and Its Modulation by Lysophosphatidylinositol in Human Breast Cancer Cells.
Int J Mol Sci
January 2025
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
2-arachnadoyl glycerol (2-AG) is one of the most common endocannabinoid molecules with anti-proliferative, cytotoxic, and pro-proliferative effects on different types of tumors. Typically, it induces cell death via cannabinoid receptor 1/2 (CB1/CB2)-linked ceramide production. In breast cancer, ceramide is counterbalanced by the sphingosine-1-phosphate, and thus the mechanisms of 2-AG influence on proliferation are poorly understood.
View Article and Find Full Text PDFHERV-W Env Induces Neuron Pyroptosis via the NLRP3-CASP1-GSDMD Pathway in Recent-Onset Schizophrenia.
Int J Mol Sci
January 2025
State Key Laboratory of Virology and Biosafety, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
HERVs (Human endogenous retroviruses) are remnants of ancient exogenous retroviruses that have integrated into the human genome, particularly in germ-line cells. Among these, the envelope protein gene (Human endogenous retroviruses W family envelope protein), located on chromosome 7 and primarily expressed in the human placenta, has been closely linked to various neuropsychiatric disorders, including schizophrenia, as well as autoimmune diseases and cancer. Recent studies have highlighted the abnormal expression of cytokines as a key factor in the pathophysiology of schizophrenia.
View Article and Find Full Text PDFCryo-EM structure of the NDH-PSI-LHCI supercomplex from Spinacia oleracea.
Nat Struct Mol Biol
January 2025
Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
The nicotinamide adenine dinucleotide phosphate (NADPH) dehydrogenase (NDH) complex is crucial for photosynthetic cyclic electron flow and respiration, transferring electrons from ferredoxin to plastoquinone while transporting H across the chloroplast membrane. This process boosts adenosine triphosphate production, regardless of NADPH levels. In flowering plants, NDH forms a supercomplex with photosystem I, enhancing its stability under high light.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!