ArticleProceedings of the National Academy of Sciences of the United States of America2005
Renouncing electroneutrality is not free of charge: switching on electrogenicity in a Na+-coupled phosphate cotransporter.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed.
- Structures of the sodium-coupled phosphate importer SLC34A2 reveal a distinct architecture and gating mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Functional role of a structural water in the elevator domain of dicarboxylate transporter VcINDY.PNAS nexus · 2026Article
- Composite Phenotype: Recurrent Nephrolithiasis and Chronic Kidney Disease in an Adult with Biallelic <italic>SLC34A3</italic> and Monoallelic <italic>SLC3A1</italic> Pathogenic Variants - Who Is "The Culprit"?Kidney & blood pressure research · 2026Article
- The "www" ofMembranes · 2022Review
- Sequence analysis and function of mosquito aeCCC2 and Drosophila Ncc83 orthologs.Insect biochemistry and molecular biology · 2022Article
- Review
- Topology, tissue distribution, and transcriptional level of SLC34s in response to Pi and pH in grass carp Ctenopharyngodon idella.Fish physiology and biochemistry · 2021Article
- Pulmonary Alveolar Microlithiasis.Seminars in respiratory and critical care medicine · 2020Review
- Evaluating pathogenicity of SLC34A3-Ser192Leu, a frequent European missense variant in disorders of renal phosphate wasting.Urolithiasis · 2019Article
- Mechanisms of phosphate transport.Nature reviews. Nephrology · 2019Review
- The molecular mechanism of SLC34 proteins: insights from two decades of transport assays and structure-function studies.Pflugers Archiv : European journal of physiology · 2019Review
- Physiological regulation of phosphate by vitamin D, parathyroid hormone (PTH) and phosphate (Pi).Pflugers Archiv : European journal of physiology · 2019Review
- Structural models of the NaPi-II sodium-phosphate cotransporters.Pflugers Archiv : European journal of physiology · 2019Review
- Effects of phospho- and calciotropic hormones on electrolyte transport in the proximal tubule.F1000Research · 2017Review
- Cation Interactions and Membrane Potential Induce Conformational Changes in NaPi-IIb.Biophysical journal · 2016Article
- Pulmonary Alveolar Microlithiasis.Clinics in chest medicine · 2016Review
- Renal control of calcium, phosphate, and magnesium homeostasis.Clinical journal of the American Society of Nephrology : CJASN · 2015Review
- Identification of the first sodium binding site of the phosphate cotransporter NaPi-IIa (SLC34A1).Biophysical journal · 2015Article
- A novel delta current method for transport stoichiometry estimation.BMC biophysics · 2014Article
- The SLC34 family of sodium-dependent phosphate transporters.Pflugers Archiv : European journal of physiology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal type IIa Na+-coupled inorganic phosphate (Pi) cotransporters (NaPi-IIa) mediate divalent Pi transport in an electrogenic manner, whereas the renal type IIc isoform (NaPi-IIc) is electroneutral, yet it shows high sequence identity with NaPi-IIa. Dual uptake (32Pi/22Na) assays confirmed that NaPi-IIc displayed Na+-coupled Pi cotransport with a 2:1 (Na+:Pi) stoichiometry compared with 3:1 established for NaPi-IIa. This finding suggested that the electrogenicity of NaPi-IIa arises from the interaction of an additional Na+ ion compared with NaPi-IIc. To identify the molecular elements responsible for the functional difference between isoforms, we used chimera and amino acid replacement approaches. Transport activity of chimeras constructed with NaPi-IIa and NaPi-IIc indicated that residues within the first six transmembrane domains were essential for the electrogenicity of NaPi-IIa. Sequence comparison between electrogenic and electroneutral isoforms revealed differences in the charge and polarity of residues clustered in three areas, one of which included part of the predicted third transmembrane domain. Here, substitution of three residues with their NaPi-IIa equivalents in NaPi-IIc (S189A, S191A, and G195D) resulted in a transporter that displayed a 1:1 charge/Pi coupling, a 3:1 Na+:Pi stoichiometry, and transient currents that resembled pre-steady-state relaxations. The mutant's weaker voltage dependency and 10-fold lower apparent Pi affinity compared with NaPi-IIa indicated that other residues important for the NaPi-IIa kinetic fingerprint exist. Our findings demonstrate that, through a minimal number of side chain substitutions, we can effect a switch from electroneutral to electrogenic cotransporter function, concomitant with the appearance of a cosubstrate interaction site.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.