Berndt, T. & Kumar, R. Phosphatonins and the regulation of phosphate homeostasis. Annu. Rev. Physiol. 69, 341â359 (2007).
Goretti Penido, M. & Alon, U. S. Phosphate homeostasis and its role in bone health. Pediatr. Nephrol. 27, 2039â2048 (2012).
Austin, S. & Mayer, A. Phosphate homeostasis â a vital metabolic equilibrium maintained through the INPHORS signaling pathway. Front. Microbiol. 11, 1367 (2020).
Giovannini, D., Touhami, J., Charnet, P., Sitbon, M. & Battini, J. L. Inorganic phosphate export by the retrovirus receptor XPR1 in metazoans. Cell Rep. 3, 1866â1873 (2013).
Li, X. et al. Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. Proc. Natl Acad. Sci. USA 117, 3568â3574 (2020).
Legati, A. et al. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat. Genet. 47, 579â581 (2015).
Anheim, M. et al. XPR1 mutations are a rare cause of primary familial brain calcification. J. Neurol. 263, 1559â1564 (2016).
Lopez-Sanchez, U. et al. Characterization of XPR1/SLC53A1 variants located outside of the SPX domain in patients with primary familial brain calcification. Sci. Rep. 9, 6776 (2019).
Berndt, T. & Kumar, R. Novel mechanisms in the regulation of phosphorus homeostasis. Physiology 24, 17â25 (2009).
Murer, H., Hernando, N., Forster, I. & Biber, J. Proximal tubular phosphate reabsorption: molecular mechanisms. Physiol. Rev. 80, 1373â1409 (2000).
Hilfiker, H. et al. Characterization of a murine type II sodium-phosphate cotransporter expressed in mammalian small intestine. Proc. Natl Acad. Sci. USA 95, 14564â14569 (1998).
Forster, I. C., Hernando, N., Biber, J. & Murer, H. Phosphate transporters of the SLC20 and SLC34 families. Mol. Aspects Med. 34, 386â395 (2013).
Wege, S. & Poirier, Y. Expression of the mammalian xenotropic polytropic virus receptor 1 (XPR1) in tobacco leaves leads to phosphate export. FEBS Lett. 588, 482â489 (2014).
Jennings, M. L. Role of transporters in regulating mammalian intracellular inorganic phosphate. Front. Pharmacol. 14, 1163442 (2023).
Ansermet, C. et al. Renal Fanconi syndrome and hypophosphatemic rickets in the absence of xenotropic and polytropic retroviral receptor in the nephron. J. Am. Soc. Nephrol. 28, 1073â1078 (2017).
Yao, X. P. et al. Analysis of gene expression and functional characterization of XPR1: a pathogenic gene for primary familial brain calcification. Cell Tissue Res. 370, 267â273 (2017).
Poirier, Y., Thoma, S., Somerville, C. & Schiefelbein, J. Mutant of Arabidopsis deficient in xylem loading of phosphate. Plant Physiol. 97, 1087â1093 (1991).
Hamburger, D., Rezzonico, E., MacDonald-Comber Petetot, J., Somerville, C. & Poirier, Y. Identification and characterization of the Arabidopsis PHO1 gene involved in phosphate loading to the xylem. Plant Cell 14, 889â902 (2002).
Poirier, Y. & Bucher, M. Phosphate transport and homeostasis in Arabidopsis. Arabidopsis Book 1, e0024 (2002).
Wang, Y., Ribot, C., Rezzonico, E. & Poirier, Y. Structure and expression profile of the Arabidopsis PHO1 gene family indicates a broad role in inorganic phosphate homeostasis. Plant Physiol. 135, 400â411 (2004).
Wege, S. et al. The EXS domain of PHO1 participates in the response of shoots to phosphate deficiency via a root-to-shoot signal. Plant Physiol. 170, 385â400 (2016).
Wild, R. et al. Control of eukaryotic phosphate homeostasis by inositol polyphosphate sensor domains. Science 352, 986â990 (2016).
Secco, D. et al. The emerging importance of the SPX domain-containing proteins in phosphate homeostasis. New Phytol. 193, 842â851 (2012).
Secco, D., Wang, C., Shou, H. & Whelan, J. Phosphate homeostasis in the yeast Saccharomyces cerevisiae, the key role of the SPX domain-containing proteins. FEBS Lett. 586, 289â295 (2012).
Puga, M. I. et al. Novel signals in the regulation of Pi starvation responses in plants: facts and promises. Curr. Opin. Plant Biol. 39, 40â49 (2017).
Jung, J. Y., Ried, M. K., Hothorn, M. & Poirier, Y. Control of plant phosphate homeostasis by inositol pyrophosphates and the SPX domain. Curr. Opin. Biotechnol. 49, 156â162 (2018).
Guan, Z. et al. Mechanistic insights into the regulation of plant phosphate homeostasis by the rice SPX2âPHR2 complex. Nat. Commun. 13, 1581 (2022).
Zhou, J. et al. Mechanism of phosphate sensing and signaling revealed by rice SPX1âPHR2 complex structure. Nat. Commun. 12, 7040 (2021).
Guan, Z. et al. The cytoplasmic synthesis and coupled membrane translocation of eukaryotic polyphosphate by signal-activated VTC complex. Nat. Commun. 14, 718 (2023).
Battini, J. L., Rasko, J. E. & Miller, A. D. A human cell-surface receptor for xenotropic and polytropic murine leukemia viruses: possible role in G protein-coupled signal transduction. Proc. Natl Acad. Sci. USA 96, 1385â1390 (1999).
Tailor, C. S., Nouri, A., Lee, C. G., Kozak, C. & Kabat, D. Cloning and characterization of a cell surface receptor for xenotropic and polytropic murine leukemia viruses. Proc. Natl Acad. Sci. USA 96, 927â932 (1999).
Yang, Y. L. et al. Receptors for polytropic and xenotropic mouse leukaemia viruses encoded by a single gene at Rmc1. Nat. Genet. 21, 216â219 (1999).
Tsai, J. Y. et al. Structure of the sodium-dependent phosphate transporter reveals insights into human solute carrier SLC20. Sci. Adv. 6, eabb4024 (2020).
Dong, Y. et al. Structure and mechanism of the human NHE1âCHP1 complex. Nat. Commun. 12, 3474 (2021).
Arakawa, T. et al. Crystal structure of the anion exchanger domain of human erythrocyte band 3. Science 350, 680â684 (2015).
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583â589 (2021).
Parker, J. L., Corey, R. A., Stansfeld, P. J. & Newstead, S. Structural basis for substrate specificity and regulation of nucleotide sugar transporters in the lipid bilayer. Nat. Commun. 10, 4657 (2019).
Capper, M. J. et al. Substrate binding and inhibition of the anion exchanger 1 transporter. Nat. Struct. Mol. Biol. 30, 1495â1504 (2023).
Guo, X. X. et al. Spectrum of SLC20A2, PDGFRB, PDGFB, and XPR1 mutations in a large cohort of patients with primary familial brain calcification. Hum. Mutat. 40, 392â403 (2019).
Drew, D. & Boudker, O. Shared molecular mechanisms of membrane transporters. Annu. Rev. Biochem. 85, 543â572 (2016).
Chen, Y. H. et al. Homologue structure of the SLAC1 anion channel for closing stomata in leaves. Nature 467, 1074â1080 (2010).
Drew, D., North, R. A., Nagarathinam, K. & Tanabe, M. Structures and general transport mechanisms by the major facilitator superfamily (MFS). Chem. Rev. 121, 5289â5335 (2021).
Gadsby, D. C., Vergani, P. & Csanady, L. The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature 440, 477â483 (2006).
Levring, J. et al. CFTR function, pathology and pharmacology at single-molecule resolution. Nature 616, 606â614 (2023).
Fairman, W. A., Vandenberg, R. J., Arriza, J. L., Kavanaugh, M. P. & Amara, S. G. An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature 375, 599â603 (1995).
Chen, I. et al. Glutamate transporters have a chloride channel with two hydrophobic gates. Nature 591, 327â331 (2021).
Gadsby, D. C. Ion channels versus ion pumps: the principal difference, in principle. Nat. Rev. Mol. Cell Biol. 10, 344â352 (2009).
Ramos, E. M. et al. Primary brain calcification: an international study reporting novel variants and associated phenotypes. Eur. J. Hum. Genet. 26, 1462â1477 (2018).
Liu, T. Y. et al. PHO2-dependent degradation of PHO1 modulates phosphate homeostasis in Arabidopsis. Plant Cell 24, 2168â2183 (2012).
Vetal, P. V. & Poirier, Y. The Arabidopsis PHOSPHATE 1 exporter undergoes constitutive internalization via clathrin-mediated endocytosis. Plant J. https://doi.org/10.1111/tpj.16441 (2023).
Rouge, L. et al. Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab. Science 367, 1224â1230 (2020).
Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331â332 (2017).
Zhang, K. Gctf: real-time CTF determination and correction. J. Struct. Biol. 193, 1â12 (2016).
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290â296 (2017).
Pettersen, E. F. et al. UCSF Chimera â a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605â1612 (2004).
Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126â2132 (2004).
Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D Struct. Biol. 74, 531â544 (2018).
Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70â82 (2021).
