Home LiteratureArticle Details
PMID: 19997129 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Sensors and regulators of intracellular pH.

Nature reviews. Molecular cell biology ·Vol. 11 ·No. 1 ·2010-01-00 ·Pages 50-61

Casey JR, Grinstein S, Orlowski J

Abstract

Protons dictate the charge and structure of macromolecules and are used as energy currency by eukaryotic cells. The unique function of individual organelles therefore depends on the establishment and stringent maintenance of a distinct pH. This, in turn, requires a means to sense the prevailing pH and to respond to deviations from the norm with effective mechanisms to transport, produce or consume proton equivalents. A dynamic, finely tuned balance between proton-extruding and proton-importing processes underlies pH homeostasis not only in the cytosol, but in other cellular compartments as well.

MeSH Terms
Animals Energy Metabolism Homeostasis Humans Hydrogen-Ion Concentration Organelles/metabolism Protons Signal Transduction Vacuolar Proton-Translocating ATPases/metabolism
Chemicals
Protons Vacuolar Proton-Translocating ATPases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Casey Joseph R
Departments of Physiology and Biochemistry, University of Alberta, Canada.
Grinstein Sergio
Orlowski John
References (122)
122 references, click to expand
  1. Bicarbonate transport in cell physiology and disease.
    Biochem J. 2009 Jan 15;417(2):423-39 PMID: 19099540
  2. The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond.
    Pflugers Arch. 2004 Feb;447(5):619-28 PMID: 12739169
  3. Role of calcium ions in regulation of mammalian intramitochondrial metabolism.
    Physiol Rev. 1990 Apr;70(2):391-425 PMID: 2157230
  4. The long physiological reach of the yeast vacuolar H+-ATPase.
    J Bioenerg Biomembr. 2007 Dec;39(5-6):415-21 PMID: 18000744
  5. Exocytosed protons feedback to suppress the Ca2+ current in mammalian cone photoreceptors.
    Neuron. 2001 Dec 20;32(6):1107-17 PMID: 11754841
  6. Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6.
    Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13854-9 PMID: 16950870
  7. Functional activation of plasma membrane anion exchangers occurs in a pre-Golgi compartment.
    J Cell Biol. 1993 Apr;121(1):37-48 PMID: 8458871
  8. Impaired acidification in early endosomes of ClC-5 deficient proximal tubule.
    Biochem Biophys Res Commun. 2005 Apr 15;329(3):941-6 PMID: 15752747
  9. Electrochemical cues regulate assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization.
    Nat Cell Biol. 2009 Mar;11(3):286-94 PMID: 19234454
  10. Calcium dynamics in the peroxisomal lumen of living cells.
    J Biol Chem. 2008 May 23;283(21):14384-90 PMID: 18362140
  11. Bicarbonate determines cytoplasmic pH and suppresses mitogen-induced alkalinization in fibroblastic cells.
    J Biol Chem. 1988 Oct 25;263(30):15253-6 PMID: 2844806
  12. Transport activity of AE3 chloride/bicarbonate anion-exchange proteins and their regulation by intracellular pH.
    Biochem J. 1999 Nov 15;344 Pt 1:221-9 PMID: 10548554
  13. 14-3-3 Binding to Na+/H+ exchanger isoform-1 is associated with serum-dependent activation of Na+/H+ exchange.
    J Biol Chem. 2001 May 11;276(19):15794-800 PMID: 11279064
  14. Molecular cloning and characterization of a novel (Na+,K+)/H+ exchanger localized to the trans-Golgi network.
    J Biol Chem. 2001 May 18;276(20):17387-94 PMID: 11279194
  15. Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers.
    J Biol Chem. 2001 May 18;276(20):17367-72 PMID: 11350981
  16. Cell migration requires both ion translocation and cytoskeletal anchoring by the Na-H exchanger NHE1.
    J Cell Biol. 2002 Dec 23;159(6):1087-96 PMID: 12486114
  17. Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology.
    Nat Rev Mol Cell Biol. 2007 Nov;8(11):917-29 PMID: 17912264
  18. Macula densa Na(+)/H(+) exchange activities mediated by apical NHE2 and basolateral NHE4 isoforms.
    Am J Physiol Renal Physiol. 2000 Mar;278(3):F452-63 PMID: 10710550
  19. Focal localization of the NHE-1 isoform of the Na+/H+ antiport: assessment of effects on intracellular pH.
    EMBO J. 1993 Dec 15;12(13):5209-18 PMID: 8262063
  20. CFTR and bicarbonate secretion by [correction of to] epithelial cells.
    News Physiol Sci. 2003 Feb;18:38-42 PMID: 12531931
  21. The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor.
    J Biol Chem. 2001 Aug 17;276(33):31349-56 PMID: 11369779
  22. Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric.
    J Biol Chem. 2004 Jul 16;279(29):30531-9 PMID: 15123620
  23. Na+/H+ exchange and pH regulation in the control of neutrophil chemokinesis and chemotaxis.
    Am J Physiol Cell Physiol. 2008 Feb;294(2):C526-34 PMID: 18094149
  24. Determinants of the pH of the Golgi complex.
    J Biol Chem. 2000 Jul 14;275(28):21025-32 PMID: 10748071
  25. The gastric HK-ATPase: structure, function, and inhibition.
    Pflugers Arch. 2009 Jan;457(3):609-22 PMID: 18536934
  26. Steady-state function of the ubiquitous mammalian Na/H exchanger (NHE1) in relation to dimer coupling models with 2Na/2H stoichiometry.
    J Gen Physiol. 2008 Oct;132(4):465-80 PMID: 18824592
  27. In situ measurements of the pH of mammalian peroxisomes using the fluorescent protein pHluorin.
    J Biol Chem. 2001 Dec 28;276(52):48748-53 PMID: 11641408
  28. Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea.
    Nat Genet. 1996 Nov;14(3):316-9 PMID: 8896562
  29. The stoichiometry of the electrogenic sodium bicarbonate cotransporter NBC1 is cell-type dependent.
    J Physiol. 2001 Mar 15;531(Pt 3):597-603 PMID: 11251043
  30. Peroxisomes in human fibroblasts have a basic pH.
    Nat Cell Biol. 2000 Jan;2(1):51-3 PMID: 10620807
  31. Calcium-binding ATPase inhibitor protein of bovine heart mitochondria. Role in ATP synthesis and effect of Ca2+.
    Biochemistry. 1989 Dec 12;28(25):9714-8 PMID: 2692714
  32. Kinetic properties of the plasma membrane Na+-H+ exchanger.
    Annu Rev Physiol. 1985;47:545-60 PMID: 2581505
  33. Proton dependence of the partial reactions of the sodium-proton exchanger in renal brush border membranes.
    J Biol Chem. 1992 Apr 25;267(12):8089-96 PMID: 1373720
  34. The Mitochondrial F0F1-ATPase proton pump is required for function of the proapoptotic protein Bax in yeast and mammalian cells.
    Mol Cell. 1998 Feb;1(3):327-36 PMID: 9660917
  35. Mouse down-regulated in adenoma (DRA) is an intestinal Cl(-)/HCO(3)(-) exchanger and is up-regulated in colon of mice lacking the NHE3 Na(+)/H(+) exchanger.
    J Biol Chem. 1999 Aug 6;274(32):22855-61 PMID: 10428871
  36. The cycling of calcium, sodium, and protons across the inner membrane of cardiac mitochondria.
    Eur J Biochem. 1978 Nov 15;91(2):599-608 PMID: 32035
  37. Organelle acidification and disease.
    Traffic. 2003 Feb;4(2):57-64 PMID: 12559032
  38. Immunocytochemical characterization of Na(+)-H+ exchanger isoform NHE-1 in rabbit kidney.
    Am J Physiol. 1992 Nov;263(5 Pt 2):F833-40 PMID: 1279986
  39. The influence of protonation states on the dynamics of the NhaA antiporter from Escherichia coli.
    Biophys J. 2007 Jun 1;92(11):3784-91 PMID: 17350999
  40. Intracellular pH sensors: design principles and functional significance.
    Physiology (Bethesda). 2007 Feb;22:30-9 PMID: 17289928
  41. Interdependent regulation of intracellular acidification and SHP-1 in apoptosis.
    Cancer Res. 1999 Apr 1;59(7):1649-54 PMID: 10197642
  42. Intracellular pH.
    Physiol Rev. 1981 Apr;61(2):296-434 PMID: 7012859
  43. Regulation of the V-ATPase in kidney epithelial cells: dual role in acid-base homeostasis and vesicle trafficking.
    J Exp Biol. 2009 Jun;212(Pt 11):1762-72 PMID: 19448085
  44. Changes in intramitochondrial and cytosolic pH: early events that modulate caspase activation during apoptosis.
    Nat Cell Biol. 2000 Jun;2(6):318-25 PMID: 10854321
  45. A molecular mechanism for aberrant CFTR-dependent HCO(3)(-) transport in cystic fibrosis.
    EMBO J. 2002 Nov 1;21(21):5662-72 PMID: 12411484
  46. Facilitation of intracellular H(+) ion mobility by CO(2)/HCO(3)(-) in rabbit ventricular myocytes is regulated by carbonic anhydrase.
    J Physiol. 2002 May 15;541(Pt 1):159-67 PMID: 12015427
  47. ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease.
    Nature. 2000 Nov 16;408(6810):369-73 PMID: 11099045
  48. Carbon dioxide permeability of aquaporin-1 measured in erythrocytes and lung of aquaporin-1 null mice and in reconstituted proteoliposomes.
    J Biol Chem. 2000 Jan 28;275(4):2686-92 PMID: 10644730
  49. Functional importance of charged residues within the putative intracellular loops in pH regulation by Na+/ H+ exchanger NHE1.
    FEBS J. 2007 Aug;274(16):4326-35 PMID: 17662110
  50. Na-H exchange-dependent increase in intracellular pH times G2/M entry and transition.
    J Biol Chem. 2003 Nov 7;278(45):44645-9 PMID: 12947095
  51. Mitochondrial cation transport systems.
    Methods Enzymol. 1995;260:331-48 PMID: 8592457
  52. Beyond ion translocation: structural functions of the sodium-hydrogen exchanger isoform-1.
    Curr Opin Nephrol Hypertens. 2007 Jul;16(4):365-72 PMID: 17565280
  53. Cytoplasmic pH, a key determinant of growth factor-induced DNA synthesis in quiescent fibroblasts.
    FEBS Lett. 1985 Oct 7;190(1):115-9 PMID: 4043390
  54. Peroxisomal lipid metabolism.
    Annu Rev Nutr. 1994;14:343-70 PMID: 7946524
  55. Functional characterization and regulation by pH of murine AE2 anion exchanger expressed in Xenopus oocytes.
    Am J Physiol. 1994 Nov;267(5 Pt 1):C1295-307 PMID: 7977693
  56. pH nanoenvironment at the surface of single melanoma cells.
    Cell Physiol Biochem. 2007;20(5):679-86 PMID: 17762194
  57. Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding protein, is expressed in intestinal epithelium.
    Biol Pharm Bull. 2003 Feb;26(2):148-55 PMID: 12576672
  58. A mechanism for the activation of the Na/H exchanger NHE-1 by cytoplasmic acidification and mitogens.
    EMBO Rep. 2004 Jan;5(1):91-6 PMID: 14710192
  59. Human homolog of mouse tescalcin associates with Na(+)/H(+) exchanger type-1.
    FEBS Lett. 2001 Nov 2;507(3):331-5 PMID: 11696366
  60. CLC chloride channels and transporters: from genes to protein structure, pathology and physiology.
    Crit Rev Biochem Mol Biol. 2008 Jan-Feb;43(1):3-36 PMID: 18307107
  61. Expression of calcineurin B homologous protein 2 protects serum deprivation-induced cell death by serum-independent activation of Na+/H+ exchanger.
    J Biol Chem. 2002 Nov 15;277(46):43771-7 PMID: 12226101
  62. Protons make tumor cells move like clockwork.
    Pflugers Arch. 2009 Sep;458(5):981-92 PMID: 19437033
  63. Decoding of cytosolic calcium oscillations in the mitochondria.
    Cell. 1995 Aug 11;82(3):415-24 PMID: 7634331
  64. Molecular physiology and genetics of Na+-independent SLC4 anion exchangers.
    J Exp Biol. 2009 Jun;212(Pt 11):1672-83 PMID: 19448077
  65. A novel carbonic anhydrase II binding site regulates NHE1 activity.
    Biochemistry. 2006 Feb 21;45(7):2414-24 PMID: 16475831
  66. Mitochondrial calcium transport: physiological and pathological relevance.
    Am J Physiol. 1994 Aug;267(2 Pt 1):C313-39 PMID: 8074170
  67. Subcellular localization of the Na+/H+ exchanger NHE1 in rat myocardium.
    Am J Physiol. 1999 Feb;276(2):H709-17 PMID: 9950874
  68. Combined computational and biochemical study reveals the importance of electrostatic interactions between the "pH sensor" and the cation binding site of the sodium/proton antiporter NhaA of Escherichia coli.
    Proteins. 2009 Aug 15;76(3):548-59 PMID: 19274728
  69. Inhibition of oxidative phosphorylation by a Ca2+-induced diminution of the adenine nucleotide translocator.
    Biochim Biophys Acta. 1983 Aug 31;724(2):278-85 PMID: 6309222
  70. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man.
    Cell. 2001 Jan 26;104(2):205-15 PMID: 11207362
  71. Apoptosis and the laws of thermodynamics.
    Nat Cell Biol. 2000 Oct;2(10):E172-3 PMID: 11025673
  72. Regulation of cell survival by Na+/H+ exchanger-1.
    Am J Physiol Renal Physiol. 2008 Sep;295(3):F625-32 PMID: 18480176
  73. Carbonic anhydrases: current state of the art, therapeutic applications and future prospects.
    J Enzyme Inhib Med Chem. 2004 Jun;19(3):199-229 PMID: 15499993
  74. Mechanisms of pH regulation in the regulated secretory pathway.
    J Biol Chem. 2001 Aug 31;276(35):33027-35 PMID: 11402049
  75. Cytoplasmic pH regulation in normal and abnormal neutrophils. Role of superoxide generation and Na+/H+ exchange.
    J Biol Chem. 1986 Jan 15;261(2):512-4 PMID: 3001067
  76. Mechanisms of pHi recovery after global ischemia in the perfused heart.
    Circ Res. 1993 May;72(5):993-1003 PMID: 8386598
  77. p90(RSK) is a serum-stimulated Na+/H+ exchanger isoform-1 kinase. Regulatory phosphorylation of serine 703 of Na+/H+ exchanger isoform-1.
    J Biol Chem. 1999 Jul 16;274(29):20206-14 PMID: 10400637
  78. A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange.
    Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12631-6 PMID: 8901634
  79. A developmentally regulated Na-H exchanger in Dictyostelium discoideum is necessary for cell polarity during chemotaxis.
    J Cell Biol. 2005 Apr 25;169(2):321-9 PMID: 15851518
  80. Multiconformation continuum electrostatics analysis of the NhaA Na+/H+ antiporter of Escherichia coli with functional implications.
    Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2629-34 PMID: 16477015
  81. Mitogen-activated protein kinase-dependent activation of the Na+/H+ exchanger is mediated through phosphorylation of amino acids Ser770 and Ser771.
    J Biol Chem. 2007 Mar 2;282(9):6292-9 PMID: 17209041
  82. Measurement of cytosolic, mitochondrial, and Golgi pH in single living cells with green fluorescent proteins.
    Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6803-8 PMID: 9618493
  83. Expression cloning and characterization of a renal electrogenic Na+/HCO3- cotransporter.
    Nature. 1997 May 22;387(6631):409-13 PMID: 9163427
  84. H(+)-gated cation channels.
    Ann N Y Acad Sci. 1999 Apr 30;868:67-76 PMID: 10414282
  85. A novel role for carbonic anhydrase: cytoplasmic pH gradient dissipation in mouse small intestinal enterocytes.
    J Physiol. 1999 Apr 1;516 ( Pt 1):209-17 PMID: 10066935
  86. Defective acidification of the biosynthetic pathway in cystic fibrosis.
    J Cell Sci Suppl. 1993;17:229-33 PMID: 7511615
  87. A specific mutation abolishing Na+/H+ antiport activity in hamster fibroblasts precludes growth at neutral and acidic pH.
    Proc Natl Acad Sci U S A. 1984 Aug;81(15):4833-7 PMID: 6087349
  88. Direct binding of the Na--H exchanger NHE1 to ERM proteins regulates the cortical cytoskeleton and cell shape independently of H(+) translocation.
    Mol Cell. 2000 Dec;6(6):1425-36 PMID: 11163215
  89. Role of the Na/H exchanger NHE1 in cell migration.
    Acta Physiol (Oxf). 2006 May-Jun;187(1-2):149-57 PMID: 16734751
  90. Local conformational fluctuations can modulate the coupling between proton binding and global structural transitions in proteins.
    Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4282-7 PMID: 15767576
  91. Intracellular pH regulation by Na(+)/H(+) exchange requires phosphatidylinositol 4,5-bisphosphate.
    J Cell Biol. 2000 Jul 10;150(1):213-24 PMID: 10893269
  92. Mutations of Arg440 and Gly455/Gly456 oppositely change pH sensing of Na+/H+ exchanger 1.
    J Biol Chem. 2003 Apr 4;278(14):11828-35 PMID: 12562776
  93. Trophic factor withdrawal: p38 mitogen-activated protein kinase activates NHE1, which induces intracellular alkalinization.
    Mol Cell Biol. 2001 Nov;21(22):7545-57 PMID: 11604491
  94. Intrinsic H(+) ion mobility in the rabbit ventricular myocyte.
    J Physiol. 2002 May 15;541(Pt 1):139-58 PMID: 12015426
  95. Growth factors activate the Na+/H+ antiporter in quiescent fibroblasts by increasing its affinity for intracellular H+.
    J Biol Chem. 1984 Sep 10;259(17):10989-94 PMID: 6088524
  96. The Na+/H+ exchanger isoform 1 (NHE1) is a novel member of the calmodulin-binding proteins. Identification and characterization of calmodulin-binding sites.
    J Biol Chem. 1994 May 6;269(18):13703-9 PMID: 8175806
  97. Cation transport systems in mitochondria: Na+ and K+ uniports and exchangers.
    J Bioenerg Biomembr. 1994 Oct;26(5):519-26 PMID: 7896767
  98. Physiological functions of plasma membrane and intracellular Ca2+ pumps revealed by analysis of null mutants.
    Ann N Y Acad Sci. 2003 Apr;986:453-60 PMID: 12763865
  99. Emerging roles of alkali cation/proton exchangers in organellar homeostasis.
    Curr Opin Cell Biol. 2007 Aug;19(4):483-92 PMID: 17646094
  100. Inhibition of Na+/H+ exchanger activity by parvovirus B19 protein NS1.
    Cell Physiol Biochem. 2009;23(1-3):211-20 PMID: 19255516
  101. Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegeneration.
    EMBO J. 2005 Mar 9;24(5):1079-91 PMID: 15706348
  102. Carbon dioxide transport through membranes.
    J Biol Chem. 2008 Sep 12;283(37):25340-25347 PMID: 18617525
  103. Intracellular acidification by inhibition of the Na+/H+-exchanger leads to caspase-independent death of cerebellar granule neurons resembling paraptosis.
    Cell Death Differ. 2004 Jul;11(7):760-70 PMID: 15017383
  104. Spatiotemporal dynamics of the ER-derived peroxisomal endomembrane system.
    Int Rev Cell Mol Biol. 2009;272:191-244 PMID: 19121819
  105. Evidence against defective trans-Golgi acidification in cystic fibrosis.
    J Biol Chem. 1996 Jun 28;271(26):15542-8 PMID: 8663158
  106. Structure and regulation of the vacuolar ATPases.
    Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):599-604 PMID: 18423392
  107. Internal pH-sensitive site couples Cl-(-)HCO3- exchange to Na+-H+ antiport in lymphocytes.
    Am J Physiol. 1989 Feb;256(2 Pt 1):C428-33 PMID: 2537575
  108. Relative CO2/NH3 selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG.
    Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5406-11 PMID: 19273840
  109. Intracellular pH regulation in heart.
    J Mol Cell Cardiol. 2009 Mar;46(3):318-31 PMID: 19041875
  110. ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL.
    J Mol Biol. 1965 May;12:88-118 PMID: 14343300
  111. p160ROCK mediates RhoA activation of Na-H exchange.
    EMBO J. 1998 Aug 17;17(16):4712-22 PMID: 9707430
  112. NHE3: a Na+/H+ exchanger isoform of renal brush border.
    Am J Physiol. 1993 Nov;265(5 Pt 2):F736-42 PMID: 8238556
  113. Contribution of the endoplasmic reticulum to peroxisome formation.
    Cell. 2005 Jul 15;122(1):85-95 PMID: 16009135
  114. Functional characterization of three isoforms of the Na+/H+ exchanger stably expressed in Chinese hamster ovary cells. ATP dependence, osmotic sensitivity, and role in cell proliferation.
    J Biol Chem. 1994 Sep 23;269(38):23544-52 PMID: 8089122
  115. CFTR regulates phagosome acidification in macrophages and alters bactericidal activity.
    Nat Cell Biol. 2006 Sep;8(9):933-44 PMID: 16921366
  116. Evolutionary origins of eukaryotic sodium/proton exchangers.
    Am J Physiol Cell Physiol. 2005 Feb;288(2):C223-39 PMID: 15643048
  117. Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2.
    Nat Genet. 2008 Jan;40(1):32-4 PMID: 18157129
  118. Mitochondrial pH monitored by a new engineered green fluorescent protein mutant.
    J Biol Chem. 2004 Mar 19;279(12):11521-9 PMID: 14701849
  119. Kinetic dissection of two distinct proton binding sites in Na+/H+ exchangers by measurement of reverse mode reaction.
    J Biol Chem. 2003 Oct 31;278(44):43580-5 PMID: 12928437
  120. The pH of the secretory pathway: measurement, determinants, and regulation.
    Physiology (Bethesda). 2004 Aug;19:207-15 PMID: 15304635
  121. Evidence for direct regulation of myocardial Na+/H+ exchanger isoform 1 phosphorylation and activity by 90-kDa ribosomal S6 kinase (RSK): effects of the novel and specific RSK inhibitor fmk on responses to alpha1-adrenergic stimulation.
    Mol Pharmacol. 2007 Mar;71(3):799-806 PMID: 17142297
  122. Regulation of pH in the mammalian central nervous system under normal and pathological conditions: facts and hypotheses.
    Neurochem Int. 2008 May;52(6):905-19 PMID: 18061308
Article Info
Journal
Nature reviews. Molecular cell biology
Abbr.
Nat Rev Mol Cell Biol
ISSN
1471-0080
DOI
10.1038/nrm2820
Published
2010-01-00
Epub
2009-00-09
Pages
50-61
Language
English
Region
England
NLM ID
100962782
Subset
IM
Grants
Canadian Institutes of Health Research · Canada
External Links
PubMed source DOI: 10.1038/nrm2820 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2