The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP
Autoři:
Flora Szeri aff001; Stefan Lundkvist aff001; Sylvia Donnelly aff001; Udo F. H. Engelke aff002; Kyu Rhee aff003; Charlene J. Williams aff004; John P. Sundberg aff005; Ron A. Wevers aff002; Ryan E. Tomlinson aff006; Robert S. Jansen aff003; Koen van de Wetering aff001
Působiště autorů:
Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania,...
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Department of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, Un
aff001; Translational Metabolic Laboratory, Department Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
aff002; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, United States of America
aff003; Cooper Medical School of Rowan University, Camden, New Jersey, United States of America
aff004; The Jackson Laboratory, Bar Harbor, Maine, United States of America
aff005; Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America
aff006
Vyšlo v časopise:
The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP. PLoS Genet 16(7): e32767. doi:10.1371/journal.pgen.1008884
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008884
Souhrn
The membrane protein ANKH was known to prevent pathological mineralization of joints and was thought to export pyrophosphate (PPi) from cells. This did not explain, however, the presence of ANKH in tissues, such as brain, blood vessels and muscle. We now report that in cultured cells ANKH exports ATP, rather than PPi, and, unexpectedly, also citrate as a prominent metabolite. The extracellular ATP is rapidly converted into PPi, explaining the role of ANKH in preventing ankylosis. Mice lacking functional Ank (Ankank/ank mice) had plasma citrate concentrations that were 65% lower than those detected in wild type control animals. Consequently, citrate excretion via the urine was substantially reduced in Ankank/ank mice. Citrate was even undetectable in the urine of a human patient lacking functional ANKH. The hydroxyapatite of Ankank/ank mice contained dramatically reduced levels of both, citrate and PPi and displayed diminished strength. Our results show that ANKH is a critical contributor to extracellular citrate and PPi homeostasis and profoundly affects bone matrix composition and, consequently, bone quality.
Klíčová slova:
Blood plasma – Bone and joint mechanics – Bone density – Cell metabolism – Femur – Homeostasis – Membrane proteins – Urine
Zdroje
1. Ho AM, Johnson MD, Kingsley DM. Role of the mouse ank gene in control of tissue calcification and arthritis. Science. 2000;289: 265–270. doi: 10.1126/science.289.5477.265 10894769
2. Kawasaki K, Buchanan AV, Weiss KM. Biomineralization in humans: making the hard choices in life. Annu Rev Genet. 2009;43: 119–142. doi: 10.1146/annurev-genet-102108-134242 19659443
3. Gurley KA, Chen H, Guenther C, Nguyen ET, Rountree RB, Schoor M, et al. Mineral formation in joints caused by complete or joint-specific loss of ANK function. J Bone Miner Res. 2006;21: 1238–1247. doi: 10.1359/jbmr.060515 16869722
4. Abhishek A, Doherty M. Pathophysiology of articular chondrocalcinosis—role of ANKH. Nat Rev Rheumatol. 2011;7: 96–104. doi: 10.1038/nrrheum.2010.182 21102543
5. Morava E, Kühnisch J, Drijvers JM, Robben JH, Cremers C, van Setten P, et al. Autosomal recessive mental retardation, deafness, ankylosis, and mild hypophosphatemia associated with a novel ANKH mutation in a consanguineous family. J Clin Endocrinol Metab. 2011;96: E189–98. doi: 10.1210/jc.2010-1539 20943778
6. Orriss IR, Arnett TR, Russell RGG. Pyrophosphate: a key inhibitor of mineralisation. Curr Opin Pharmacol. 2016;28: 57–68. doi: 10.1016/j.coph.2016.03.003 27061894
7. Nitschke Y, Rutsch F. Inherited Arterial Calcification Syndromes: Etiologies and Treatment Concepts. Curr Osteoporos Rep. 2017;15: 1–16. doi: 10.1007/s11914-017-0341-8 28110469
8. Jansen RS, Küçükosmanoglu A, de Haas M, Sapthu S, Otero JA, Hegman IEM, et al. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci USA. 2013;110: 20206–20211. doi: 10.1073/pnas.1319582110 24277820
9. Jansen RS, Duijst S, Mahakena S, Sommer D, Szeri F, Váradi A, et al. ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report. Arterioscler Thromb Vasc Biol 2014;34: 1985–1989. doi: 10.1161/ATVBAHA.114.304017 24969777
10. Goncalves MD, Lu C, Tutnauer J, Hartman TE, Hwang S-K, Murphy CJ, et al. High-fructose corn syrup enhances intestinal tumor growth in mice. Science. 2019;363: 1345–1349. doi: 10.1126/science.aat8515 30898933
11. Kim HJ, Minashima T, McCarthy EF, Winkles JA, Kirsch T. Progressive ankylosis protein (ANK) in osteoblasts and osteoclasts controls bone formation and bone remodeling. J Bone Miner Res. 2010;25: 1771–1783. doi: 10.1002/jbmr.60 20200976
12. Alfrey AC, Solomons CC. Bone pyrophosphate in uremia and its association with extraosseous calcification. J Clin Invest. 1976;57: 700–705. doi: 10.1172/JCI108327 175092
13. Mycielska ME, Milenkovic VM, Wetzel CH, Rümmele P, Geissler EK. Extracellular Citrate in Health and Disease. Curr Mol Med. 2015;15: 884–891. doi: 10.2174/1566524016666151123104855 26592250
14. Petrarulo M, Facchini P, Cerelli E, Marangella M, Linari F. Citrate in urine determined with a new citrate lyase method. Clin Chem. 1995;41: 1518–1521. 7586527
15. Hu Y-Y, Rawal A, Schmidt-Rohr K. Strongly bound citrate stabilizes the apatite nanocrystals in bone. Proc Natl Acad Sci USA. 2010;107: 22425–22429. doi: 10.1073/pnas.1009219107 21127269
16. Ma C, Tian X, Kim JP, Xie D, Ao X, Shan D, et al. Citrate-based materials fuel human stem cells by metabonegenic regulation. Proc Natl Acad Sci USA. 2018;115: E11741–E11750. doi: 10.1073/pnas.1813000115 30478052
17. Shin S-Y, Fauman EB, Petersen A-K, Krumsiek J, Santos R, Huang J, et al. An atlas of genetic influences on human blood metabolites. Nat Genet. 2014;46: 543–550. doi: 10.1038/ng.2982 24816252
18. Klein MS, Almstetter MF, Nürnberger N, Sigl G, Gronwald W, Wiedemann S, et al. Correlations between milk and plasma levels of amino and carboxylic acids in dairy cows. J Proteome Res. 2013;12: 5223–5232. doi: 10.1021/pr4006537 23931703
19. Iacobazzi V, Infantino V. Citrate—new functions for an old metabolite. Biol Chem. 2014;395: 387–399. doi: 10.1515/hsz-2013-0271 24445237
20. Rudman D, Dedonis JL, Fountain MT, Chandler JB, Gerron GG, Fleming GA, et al. Hypocitraturia in patients with gastrointestinal malabsorption. N Engl J Med. 1980;303: 657–661. doi: 10.1056/NEJM198009183031201 7402252
21. Birkenfeld AL, Lee H-Y, Guebre-Egziabher F, Alves TC, Jurczak MJ, Jornayvaz FR, et al. Deletion of the mammalian INDY homolog mimics aspects of dietary restriction and protects against adiposity and insulin resistance in mice. Cell Metabolism. 2011;14: 184–195. doi: 10.1016/j.cmet.2011.06.009 21803289
22. Mycielska ME, Sun H, Dettmer K, Rümmele P, Schmidt K, Prehn C, et al. Extracellular Citrate Affects Critical Elements of Cancer Cell Metabolism and Supports Cancer Development In Vivo. Cancer Res. 2018;78: 2513–2523. doi: 10.1158/0008-5472.CAN-17-2959 29510993
23. Raffin EP, Penniston KL, Antonelli JA, Viprakasit DP, Averch TD, Bird VG, et al. The Effect of Thiazide and Potassium Citrate Use on the Health Related Quality of Life of Patients with Urolithiasis. J Urol. 2018;200: 1290–1294. doi: 10.1016/j.juro.2018.06.023 29913138
24. Harvey JA, Zobitz MM, Pak CY. Bioavailability of citrate from two different preparations of potassium citrate. J Clin Pharmacol. 1989;29: 338–341. doi: 10.1002/j.1552-4604.1989.tb03338.x 2723122
25. Pajor AM. Sodium-coupled dicarboxylate and citrate transporters from the SLC13 family. Pflugers Arch. 2014;466: 119–130. doi: 10.1007/s00424-013-1369-y 24114175
26. Goraya N, Simoni J, Sager LN, Madias NE, Wesson DE. Urine citrate excretion as a marker of acid retention in patients with chronic kidney disease without overt metabolic acidosis. Kidney Int. 2019;95: 1190–1196. doi: 10.1016/j.kint.2018.11.033 30846270
27. Rosenthal AK, Gohr CM, Mitton-Fitzgerald E, Lutz MK, Dubyak GR, Ryan LM. The progressive ankylosis gene product ANK regulates extracellular ATP levels in primary articular chondrocytes. Arthritis Res Ther. 2013;15: R154. doi: 10.1186/ar4337 24286344
28. Costello JC, Rosenthal AK, Kurup IV, Masuda I, Medhora M, Ryan LM. Parallel regulation of extracellular ATP and inorganic pyrophosphate: roles of growth factors, transduction modulators, and ANK. Connect Tissue Res. 2011;52: 139–146. doi: 10.3109/03008207.2010.491928 20604715
29. Mitton-Fitzgerald E, Gohr CM, Bettendorf B, Rosenthal AK. The Role of ANK in Calcium Pyrophosphate Deposition Disease. Curr Rheumatol Rep. 2016;18: 25. doi: 10.1007/s11926-016-0574-z 27032788
30. Kato K, Nishimasu H, Okudaira S, Mihara E, Ishitani R, Takagi J, et al. Crystal structure of Enpp1, an extracellular glycoprotein involved in bone mineralization and insulin signaling. Proc Natl Acad Sci USA. 2012;109: 16876–16881. doi: 10.1073/pnas.1208017109 23027977
31. Huesa C, Staines KA, Millán JL, MacRae VE. Effects of etidronate on the Enpp1−/− mouse model of generalized arterial calcification of infancy. Int J Mol Med. 2015;36: 159–165. doi: 10.3892/ijmm.2015.2212 25975272
32. Albright RA, Stabach P, Cao W, Kavanagh D, Mullen I, Braddock AA, et al. ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy. Nature Commun. 2015;6: 10006. doi: 10.1038/ncomms10006 26624227
33. Li Q, Guo H, Chou DW, Berndt A, Sundberg JP, Uitto J. Mutant Enpp1asj mice as a model for generalized arterial calcification of infancy. Dis Models Mech. 2013;6: 1227–1235. doi: 10.1242/dmm.012765 23798568
34. Russell RGG. Bisphosphonates: From Bench to Bedside. Ann N Y Acad Sci. 2006;1068: 367–401. doi: 10.1196/annals.1346.041 16831938
35. Dedinszki D, Szeri F, Kozák E, Pomozi V, Tőkési N, Mezei TR, et al. Oral administration of pyrophosphate inhibits connective tissue calcification. EMBO Mol Med. 2017;9: 1463–1470. doi: 10.15252/emmm.201707532 28701330
36. Uitto J, Li Q, van de Wetering K, Váradi A, Terry SF. Insights into Pathomechanisms and Treatment Development in Heritable Ectopic Mineralization Disorders: Summary of the PXE International Biennial Research Symposium-2016. J Invest Dermatol. 2017;137: 790–795. doi: 10.1016/j.jid.2016.12.014 28340679
37. Borst P, Váradi A, van de Wetering K. PXE, a Mysterious Inborn Error Clarified. Trends Biochem Sci. 2019;44: 125–140. doi: 10.1016/j.tibs.2018.10.005 30446375
38. Mazurek MP, Prasad PD, Gopal E, Fraser SP, Bolt L, Rizaner N, et al. Molecular origin of plasma membrane citrate transporter in human prostate epithelial cells. EMBO reports. EMBO Press; 2010;11: 431–437. doi: 10.1038/embor.2010.51 20448665
39. Engelke UFH, Tassini M, Hayek J, de Vries M, Bilos A, Vivi A, et al. Guanidinoacetate methyltransferase (GAMT) deficiency diagnosed by proton NMR spectroscopy of body fluids. NMR Biomed. 2009;22: 538–544. doi: 10.1002/nbm.1367 19288536
40. Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. 2010;25: 1468–1486. doi: 10.1002/jbmr.141 20533309
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