Home LiteratureArticle Details
PMID: 17473931 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Visualization and manipulation of phosphoinositide dynamics in live cells using engineered protein domains.

Pflugers Archiv : European journal of physiology ·Vol. 455 ·No. 1 ·2007-10-00 ·Pages 69-82

Várnai P, Balla T

Abstract

There is hardly a membrane-associated molecular event that is not regulated by phosphoinositides, a minor but critically important class of phospholipids of cellular membranes. The rapid formation, elimination, and conversion of these lipids in specific membrane compartments are ensured by a wealthy number of inositol lipid kinases and phosphatases with unique localization and regulatory properties. The existence of multiple inositol lipid pools have been indicated by metabolic labeling studies, but the level of functional compartmentalization revealed by the identification of numerous protein effectors acted upon by phosphoinositides could not have been foreseen. The changing perception of inositides from just serving as lipid precursors of second messengers to becoming highly dynamic local membrane-bound regulators poses new challenges concerning the detection of their rapid localized changes. Moreover, it is increasingly evident that manipulation of lipids in highly defined compartments would be a highly superior approach to soaking the cells with a particular phosphoinositide when studying the local regulation of the lipid on any effectors. In this review, we will summarize our efforts to improve our tools in studying phosphoinositide dynamics and discuss our views on the values of these methods compared to other options currently used or being explored.

MeSH Terms
Animals Cell Membrane/metabolism,ultrastructure Cells/metabolism,ultrastructure Humans Inositol Phosphates/metabolism Microscopy, Confocal Phosphatidylinositols/metabolism Protein Engineering Recombinant Proteins/pharmacology
Chemicals
Inositol Phosphates Phosphatidylinositols Recombinant Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Várnai Péter
Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bldg 49, Rm 6A35, 49 Convent Drive, Bethesda, MD, USA. [email protected]
Balla Tamas
References (108)
108 references, click to expand
  1. Fluorescent biosensor for quantitative real-time measurements of inositol 1,4,5-trisphosphate in single living cells.
    J Biol Chem. 2004 Sep 10;279(37):38095-8 PMID: 15272011
  2. Polarity in intracellular calcium signaling.
    Bioessays. 1999 Oct;21(10):851-60 PMID: 10497335
  3. Insulin-dependent translocation of ARNO to the plasma membrane of adipocytes requires phosphatidylinositol 3-kinase.
    Curr Biol. 1998 Apr 9;8(8):463-6 PMID: 9550703
  4. Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities.
    Biochem J. 2000 Oct 1;351(Pt 1):19-31 PMID: 11001876
  5. PtdIns(3)P regulates the neutrophil oxidase complex by binding to the PX domain of p40(phox).
    Nat Cell Biol. 2001 Jul;3(7):679-82 PMID: 11433301
  6. G-protein signaling through tubby proteins.
    Science. 2001 Jun 15;292(5524):2041-50 PMID: 11375483
  7. A comparative analysis of the phosphoinositide binding specificity of pleckstrin homology domains.
    J Biol Chem. 1997 Aug 29;272(35):22059-66 PMID: 9268346
  8. Inositol phospholipids and cell surface receptor function.
    Biochim Biophys Acta. 1975 Mar 25;415(1):81-47 PMID: 164246
  9. Intracellular delivery of phosphoinositides and inositol phosphates using polyamine carriers.
    Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11286-91 PMID: 11005844
  10. Phosphatidylinositol 3,5-bisphosphate: metabolism and cellular functions.
    Trends Biochem Sci. 2006 Jan;31(1):52-63 PMID: 16364647
  11. Akt/PKB localisation and 3' phosphoinositide generation at sites of epithelial cell-matrix and cell-cell interaction.
    Curr Biol. 1999 Apr 22;9(8):433-6 PMID: 10226029
  12. Evidence that the tandem-pleckstrin-homology-domain-containing protein TAPP1 interacts with Ptd(3,4)P2 and the multi-PDZ-domain-containing protein MUPP1 in vivo.
    Biochem J. 2002 Feb 1;361(Pt 3):525-36 PMID: 11802782
  13. EEA1 links PI(3)K function to Rab5 regulation of endosome fusion.
    Nature. 1998 Jul 30;394(6692):494-8 PMID: 9697774
  14. The relationship of hormone-sensitive and hormone-insensitive phosphatidylinositol to phosphatidylinositol 4,5-bisphosphate in the WRK-1 cell.
    J Biol Chem. 1986 Jan 5;261(1):88-91 PMID: 3001064
  15. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling.
    Cell. 2006 May 19;125(4):733-47 PMID: 16647110
  16. EGF-and NGF-stimulated translocation of cytohesin-1 to the plasma membrane of PC12 cells requires PI 3-kinase activation and a functional cytohesin-1 PH domain.
    J Cell Sci. 1999 Jun;112 ( Pt 12):1957-65 PMID: 10341214
  17. How accurately can we image inositol lipids in living cells?
    Trends Pharmacol Sci. 2000 Jul;21(7):238-41 PMID: 10871889
  18. Differential PI 3-kinase dependence of early and late phases of recycling of the internalized AT1 angiotensin receptor.
    J Cell Biol. 2002 Jun 24;157(7):1211-22 PMID: 12070129
  19. Nuclear inositide signalling -- expansion, structures and clarification.
    Biochim Biophys Acta. 2006 May-Jun;1761(5-6):505-8 PMID: 16574480
  20. Decoding of cytosolic calcium oscillations in the mitochondria.
    Cell. 1995 Aug 11;82(3):415-24 PMID: 7634331
  21. Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi.
    Cell. 2003 Aug 8;114(3):299-310 PMID: 12914695
  22. Selective cellular effects of overexpressed pleckstrin-homology domains that recognize PtdIns(3,4,5)P3 suggest their interaction with protein binding partners.
    J Cell Sci. 2005 Oct 15;118(Pt 20):4879-88 PMID: 16219693
  23. Mammalian phosphatidylinositol transfer proteins: emerging roles in signal transduction and vesicular traffic.
    Chem Phys Lipids. 1999 Apr;98(1-2):23-33 PMID: 10358925
  24. Ent3p Is a PtdIns(3,5)P2 effector required for protein sorting to the multivesicular body.
    Dev Cell. 2003 Sep;5(3):499-511 PMID: 12967568
  25. Analysis of the metabolic turnover of the individual phosphate groups of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate. Validation of novel analytical techniques by using 32P-labelled lipids from erythrocytes.
    Biochem J. 1984 Mar 15;218(3):785-93 PMID: 6326746
  26. Targeting of inositol 1,4,5-trisphosphate receptors to the endoplasmic reticulum by multiple signals within their transmembrane domains.
    J Biol Chem. 2004 May 28;279(22):23797-805 PMID: 15033979
  27. Regulation of calcium signals in the nucleus by a nucleoplasmic reticulum.
    Nat Cell Biol. 2003 May;5(5):440-6 PMID: 12717445
  28. The pleckstrin homology domains of protein kinase B and GRP1 (general receptor for phosphoinositides-1) are sensitive and selective probes for the cellular detection of phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 3,4,5-trisphosphate in vivo.
    Biochem J. 1999 Dec 15;344 Pt 3:929-36 PMID: 10585883
  29. An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways.
    Nat Methods. 2005 Jun;2(6):415-8 PMID: 15908919
  30. Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate.
    Science. 1997 Jan 31;275(5300):665-8 PMID: 9005852
  31. Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells.
    EMBO J. 2000 Sep 1;19(17):4577-88 PMID: 10970851
  32. Myo-inositol phosphates from beef brain phosphoinostide.
    J Biol Chem. 1960 Jun;235:PC23-4 PMID: 13828720
  33. Targeted expression of the inositol 1,4,5-triphosphate receptor (IP3R) ligand-binding domain releases Ca2+ via endogenous IP3R channels.
    Proc Natl Acad Sci U S A. 2005 May 31;102(22):7859-64 PMID: 15911776
  34. Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1.
    Nat Cell Biol. 2007 Jan;9(1):36-44 PMID: 17173042
  35. Control of calcium signal propagation to the mitochondria by inositol 1,4,5-trisphosphate-binding proteins.
    J Biol Chem. 2005 Apr 1;280(13):12820-32 PMID: 15644334
  36. Inositol trisphosphate, a novel second messenger in cellular signal transduction.
    Nature. 1984 Nov 22-28;312(5992):315-21 PMID: 6095092
  37. Phosphatidylinositol 4,5-bisphosphate functions as a second messenger that regulates cytoskeleton-plasma membrane adhesion.
    Cell. 2000 Jan 21;100(2):221-8 PMID: 10660045
  38. Monitoring agonist-induced phospholipase C activation in live cells by fluorescence resonance energy transfer.
    J Biol Chem. 2001 May 4;276(18):15337-44 PMID: 11152673
  39. Transforming protein of avian sarcoma virus UR2 is associated with phosphatidylinositol kinase activity: possible role in tumorigenesis.
    Proc Natl Acad Sci U S A. 1984 May;81(9):2728-32 PMID: 6326140
  40. Mutational analysis of Gbetagamma and phospholipid interaction with G protein-coupled receptor kinase 2.
    J Biol Chem. 2000 Apr 7;275(14):10443-52 PMID: 10744734
  41. Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains.
    EMBO J. 2004 Oct 1;23(19):3711-20 PMID: 15359279
  42. Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma.
    Science. 2003 May 23;300(5623):1256-62 PMID: 12764189
  43. Rapidly inducible changes in phosphatidylinositol 4,5-bisphosphate levels influence multiple regulatory functions of the lipid in intact living cells.
    J Cell Biol. 2006 Nov 6;175(3):377-82 PMID: 17088424
  44. Evidence that the inositol phospholipids are necessary for exocytosis. Loss of inositol phospholipids and inhibition of secretion in permeabilized cells caused by a bacterial phospholipase C and removal of ATP.
    Biochem J. 1990 May 15;268(1):15-25 PMID: 2160809
  45. The PH domain and the polybasic c domain of cytohesin-1 cooperate specifically in plasma membrane association and cellular function.
    Mol Biol Cell. 1998 Aug;9(8):1981-94 PMID: 9693361
  46. The PX domains of p47phox and p40phox bind to lipid products of PI(3)K.
    Nat Cell Biol. 2001 Jul;3(7):675-8 PMID: 11433300
  47. Phosphoinositides, key molecules for regulation of actin cytoskeletal organization and membrane traffic from the plasma membrane.
    Biochim Biophys Acta. 2001 Oct 31;1533(3):190-206 PMID: 11731330
  48. Phosphatidylinositol 3-kinase-dependent membrane association of the Bruton's tyrosine kinase pleckstrin homology domain visualized in single living cells.
    J Biol Chem. 1999 Apr 16;274(16):10983-9 PMID: 10196179
  49. Targeting of Golgi-specific pleckstrin homology domains involves both PtdIns 4-kinase-dependent and -independent components.
    Curr Biol. 2002 Apr 30;12(9):695-704 PMID: 12007412
  50. The role of the phosphoinositides at the Golgi complex.
    Biochim Biophys Acta. 2005 Jul 10;1744(3):396-405 PMID: 15979509
  51. Active Arf6 recruits ARNO/cytohesin GEFs to the PM by binding their PH domains.
    Mol Biol Cell. 2007 Jun;18(6):2244-53 PMID: 17409355
  52. Essential role of phosphoinositide metabolism in synaptic vesicle recycling.
    Cell. 1999 Oct 15;99(2):179-88 PMID: 10535736
  53. Specific and high-affinity binding of inositol phosphates to an isolated pleckstrin homology domain.
    Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10472-6 PMID: 7479822
  54. Imaging phosphoinositide dynamics using GFP-tagged protein domains.
    Biol Cell. 2005 Jul;97(7):501-18 PMID: 15966865
  55. The FYVE domain of early endosome antigen 1 is required for both phosphatidylinositol 3-phosphate and Rab5 binding. Critical role of this dual interaction for endosomal localization.
    J Biol Chem. 2000 Feb 4;275(5):3699-705 PMID: 10652369
  56. A 15-residue bifunctional element in D-AKAP1 is required for both endoplasmic reticulum and mitochondrial targeting.
    J Biol Chem. 2002 Jul 26;277(30):27328-36 PMID: 11994283
  57. Mitochondrial Ca2+ uptake with and without the formation of high-Ca2+ microdomains.
    Cell Calcium. 2006 Nov-Dec;40(5-6):527-37 PMID: 17069884
  58. Nerve growth factor- and epidermal growth factor-stimulated translocation of the ADP-ribosylation factor-exchange factor GRP1 to the plasma membrane of PC12 cells requires activation of phosphatidylinositol 3-kinase and the GRP1 pleckstrin homology domain.
    Biochem J. 1998 Oct 1 ;335 ( Pt 1):139-46 PMID: 9742223
  59. Coincidence detection in phosphoinositide signaling.
    Trends Cell Biol. 2005 Oct;15(10):540-7 PMID: 16139503
  60. Visualizing PI3 kinase-mediated cell-cell signaling during Dictyostelium development.
    Curr Biol. 2002 Jul 23;12(14):1178-88 PMID: 12176327
  61. PtdIns(4,5)P2 functions at the cleavage furrow during cytokinesis.
    Curr Biol. 2005 Aug 9;15(15):1407-12 PMID: 16085494
  62. Rapid chemically induced changes of PtdIns(4,5)P2 gate KCNQ ion channels.
    Science. 2006 Dec 1;314(5804):1454-7 PMID: 16990515
  63. Dual effect of beta-adrenergic receptors on mitogen-activated protein kinase. Evidence for a beta gamma-dependent activation and a G alpha s-cAMP-mediated inhibition.
    J Biol Chem. 1995 Oct 20;270(42):25259-65 PMID: 7559665
  64. A novel recombinant hyperaffinity inositol 1,4,5-trisphosphate (IP(3)) absorbent traps IP(3), resulting in specific inhibition of IP(3)-mediated calcium signaling.
    J Biol Chem. 2002 Mar 8;277(10):8106-13 PMID: 11741904
  65. Visualization of phosphoinositides that bind pleckstrin homology domains: calcium- and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools.
    J Cell Biol. 1998 Oct 19;143(2):501-10 PMID: 9786958
  66. The pleckstrin homology domain of oxysterol-binding protein recognises a determinant specific to Golgi membranes.
    Curr Biol. 1998 Jun 18;8(13):729-39 PMID: 9651677
  67. Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate.
    Nature. 1988 Apr 14;332(6165):644-6 PMID: 2833705
  68. Compartmental signal modulation: Endosomal phosphatidylinositol 3-phosphate controls endosome morphology and selective cargo sorting.
    Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15473-8 PMID: 17030795
  69. Receptor-induced transient reduction in plasma membrane PtdIns(4,5)P2 concentration monitored in living cells.
    Curr Biol. 1998 Mar 12;8(6):343-6 PMID: 9512420
  70. Genome-wide analysis of membrane targeting by S. cerevisiae pleckstrin homology domains.
    Mol Cell. 2004 Mar 12;13(5):677-88 PMID: 15023338
  71. Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt.
    Mol Cell Biol. 1998 Jul;18(7):4131-40 PMID: 9632797
  72. Single cell imaging of PI3K activity and glucose transporter insertion into the plasma membrane by dual color evanescent wave microscopy.
    Sci STKE. 2003 Feb 11;2003(169):PL4 PMID: 12582202
  73. Distinct polyphosphoinositide binding selectivities for pleckstrin homology domains of GRP1-like proteins based on diglycine versus triglycine motifs.
    J Biol Chem. 2000 Oct 20;275(42):32816-21 PMID: 10913124
  74. Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 in the nucleation of clathrin lattices on membranes.
    Science. 2001 Feb 9;291(5506):1051-5 PMID: 11161218
  75. A wave of IP3 production accompanies the fertilization Ca2+ wave in the egg of the frog, Xenopus laevis: theoretical and experimental support.
    Cell Calcium. 2004 May;35(5):433-47 PMID: 15003853
  76. Phosphatidylinositol 3-phosphate recognition by the FYVE domain.
    Mol Cell. 1999 Jun;3(6):805-11 PMID: 10394369
  77. Receptor activation alters inner surface potential during phagocytosis.
    Science. 2006 Jul 21;313(5785):347-51 PMID: 16857939
  78. Phosphoinositide regulation of the actin cytoskeleton.
    Annu Rev Physiol. 2003;65:761-89 PMID: 12471164
  79. Pleckstrin homology domains: not just for phosphoinositides.
    Biochem Soc Trans. 2004 Nov;32(Pt 5):707-11 PMID: 15493994
  80. GTP hydrolysis by ADP-ribosylation factor is dependent on both an ADP-ribosylation factor GTPase-activating protein and acid phospholipids.
    J Biol Chem. 1994 Apr 8;269(14):10758-63 PMID: 8144664
  81. Live cell imaging of phosphoinositide dynamics with fluorescent protein domains.
    Biochim Biophys Acta. 2006 Aug;1761(8):957-67 PMID: 16702024
  82. Polarization of chemoattractant receptor signaling during neutrophil chemotaxis.
    Science. 2000 Feb 11;287(5455):1037-40 PMID: 10669415
  83. Synthesis and biological activity of phospholipase C-resistant analogues of phosphatidylinositol 4,5-bisphosphate.
    J Am Chem Soc. 2006 May 3;128(17):5642-3 PMID: 16637624
  84. Phospholipase C in living cells: activation, inhibition, Ca2+ requirement, and regulation of M current.
    J Gen Physiol. 2005 Sep;126(3):243-62 PMID: 16129772
  85. A plasma membrane pool of phosphatidylinositol 4-phosphate is generated by phosphatidylinositol 4-kinase type-III alpha: studies with the PH domains of the oxysterol binding protein and FAPP1.
    Mol Biol Cell. 2005 Mar;16(3):1282-95 PMID: 15635101
  86. Multiple pools of phosphatidylinositol 4-phosphate detected using the pleckstrin homology domain of Osh2p.
    J Biol Chem. 2004 Oct 22;279(43):44683-9 PMID: 15271978
  87. Mutational analysis of the ligand binding site of the inositol 1,4,5-trisphosphate receptor.
    J Biol Chem. 1996 Jul 26;271(30):18277-84 PMID: 8663526
  88. Distinct specificity in the recognition of phosphoinositides by the pleckstrin homology domains of dynamin and Bruton's tyrosine kinase.
    EMBO J. 1996 Nov 15;15(22):6241-50 PMID: 8947047
  89. Enzyme secretion and the incorporation of P32 into phospholipides of pancreas slices.
    J Biol Chem. 1953 Aug;203(2):967-77 PMID: 13084667
  90. Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing pleckstrin and Sec7 homology domains.
    Science. 1997 Mar 28;275(5308):1927-30 PMID: 9072969
  91. New insights into the molecular and cellular workings of the cardiac Na+/Ca2+ exchanger.
    Am J Physiol Cell Physiol. 2004 Nov;287(5):C1167-72 PMID: 15475515
  92. Receptor-mediated regulation of PI3Ks confines PI(3,4,5)P3 to the leading edge of chemotaxing cells.
    Mol Biol Cell. 2003 May;14 (5):1913-22 PMID: 12802064
  93. Subcellular localization of phosphatidylinositol 4,5-bisphosphate using the pleckstrin homology domain of phospholipase C delta1.
    Biochem J. 2002 May 1;363(Pt 3):657-66 PMID: 11964166
  94. Probing phosphoinositide functions in signaling and membrane trafficking.
    Trends Cell Biol. 2005 May;15(5):259-68 PMID: 15866030
  95. Localization of a high-affinity inositol 1,4,5-trisphosphate/inositol 1,4,5,6-tetrakisphosphate binding domain to the pleckstrin homology module of a new 130 kDa protein: characterization of the determinants of structural specificity.
    Biochem J. 1996 Sep 1;318 ( Pt 2):561-8 PMID: 8809047
  96. Inositol lipid binding and membrane localization of isolated pleckstrin homology (PH) domains. Studies on the PH domains of phospholipase C delta 1 and p130.
    J Biol Chem. 2002 Jul 26;277(30):27412-22 PMID: 12019260
  97. Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates.
    EMBO J. 2004 Oct 13;23(20):3918-28 PMID: 15457207
  98. Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers.
    Mol Cell Biol. 1999 Oct;19(10 ):6845-57 PMID: 10490623
  99. Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains.
    Mol Cell. 1998 Jul;2(1):157-62 PMID: 9702203
  100. The effector domain of myristoylated alanine-rich C kinase substrate binds strongly to phosphatidylinositol 4,5-bisphosphate.
    J Biol Chem. 2001 Feb 16;276(7):5012-9 PMID: 11053422
  101. Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors.
    EMBO J. 2004 May 5;23 (9):1922-33 PMID: 15103325
  102. Golgi retention mechanism of beta-1,4-galactosyltransferase. Membrane-spanning domain-dependent homodimerization and association with alpha- and beta-tubulins.
    J Biol Chem. 1995 May 19;270(20):12170-6 PMID: 7744867
  103. Detection of novel intracellular agonist responsive pools of phosphatidylinositol 3,4-bisphosphate using the TAPP1 pleckstrin homology domain in immunoelectron microscopy.
    Biochem J. 2004 Feb 1;377(Pt 3):653-63 PMID: 14604433
  104. Similarities in function and gene structure of cytohesin-4 and cytohesin-1, guanine nucleotide-exchange proteins for ADP-ribosylation factors.
    J Biol Chem. 2000 Feb 4;275(5):3221-30 PMID: 10652308
  105. FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P.
    Nat Cell Biol. 2004 May;6(5):393-404 PMID: 15107860
  106. ATP-dependent inositide phosphorylation required for Ca(2+)-activated secretion.
    Nature. 1995 Mar 9;374(6518):173-7 PMID: 7877690
  107. PI(3,4,5)P3 and PI(4,5)P2 lipids target proteins with polybasic clusters to the plasma membrane.
    Science. 2006 Dec 1;314(5804):1458-61 PMID: 17095657
  108. Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels.
    J Cell Biol. 2006 Dec 18;175(6):901-11 PMID: 17178908
Article Info
Journal
Pflugers Archiv : European journal of physiology
Abbr.
Pflugers Arch
ISSN
0031-6768
Published
2007-10-00
Epub
2007-00-01
Pages
69-82
Language
English
Region
Germany
NLM ID
0154720
Subset
IM
Grants
Intramural NIH HHS · United States
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]