Dr Lynda Partridge
Tel: 0114 222 4185
Tetraspanins in health and disease
Tetraspanins constitute a highly conserved superfamily of transmembrane proteins, with the first member having appeared some 570 million years ago. They are widely expressed in multicellular organisms and are involved in basic cell functions such as motility, fusion and membrane trafficking. Tetraspanins are distinguished from other four-pass membrane proteins by the presence of conserved charged residues in the transmembrane domains and a defining “signature” motif in the larger of the two extracellular domains. Characteristically, they form promiscuous associations with one another and with other membrane proteins and lipids to generate a specialised type of microdomain: the tetraspanin enriched microdomain (TEM). As components of TEMs, tetraspanins maintain a network of interactions with other membrane proteins (e.g. integrins, signalling molecules), regulating the assembly of multi-molecular signalling platforms.
There are 33 tetraspanins in mammals and they have been implicated in fertilisation, the immune response, cancer progression and pathogen susceptibility. Our group is using specific antibodies, recombinant proteins and site-directed mutagenesis to investigate the role of tetraspanins in health and disease. We have recently demonstrated that tetraspanins are involved in controlling the formation of multinucleated giant cells (MNGCs), which are associated with chronic inflammation and certain types of infection. We are also studying tetraspanin function using a zebrafish embryo model, using morpholinos and the CRISPR/Cas9 system to knock down or knock out specific zebrafish tetraspanin genes, which show remarkable conservation with humans. After finding that they are involved in bacterial infections, we are also currently developing tetraspanin-based reagents as alternatives to antibiotics for treating infections caused by microbes such as Staphylococcus aureus (including MRSA).
Antibodies in research
I have also had a long-standing interest in the production and use of antibodies as tools in research and medicine. In the early 1990s, I helped establish a dedicated facility at the University for custom production of antibodies for researchers. A related spin-out company, Bioserv UK Ltd, was established in 2009, which specialises in the production of antibodies and other proteins from mammalian cell culture.
Eukaryotic cell biology, immunology, tetraspanins, antibodies
Level 4 Modules
MBB405 Advanced Research Topics
Level 3 Modules
MBB303 Cells as Factories
Level 2 Modules
MBB263 Microbiology 2
Level 1 Modules
Honours and Distinctions
- Correction to: A role for tetraspanin proteins in regulating fusion induced by Burkholderia thailandensis.. Med Microbiol Immunol.
- Establishing a Porcine Ex Vivo Cornea Model for Studying Drug Treatments against Bacterial Keratitis. Journal of Visualized Experiments.
- A role for tetraspanin proteins in regulating fusion induced by Burkholderia thailandensis. Medical Microbiology and Immunology. View this article in WRRO
- Characterization of ocular clinical isolates of Pseudomonas aeruginosa from non-contact lens related keratitis patients from south India. Microorganisms, 8(2). View this article in WRRO
- Monocyte Subsets Have Distinct Patterns of Tetraspanin Expression and Different Capacities to Form Multinucleate Giant Cells. Frontiers in Immunology, 9. View this article in WRRO
- A role for the tetraspanin proteins in Salmonella infection of human macrophages. Journal of Infection, 75(2), 115-124. View this article in WRRO
- Tspan2: a tetraspanin protein involved in oligodendrogenesis and cancer metastasis.. Biochem Soc Trans, 45(2), 465-475. View this article in WRRO
- Peptides from Tetraspanin CD9 Are Potent Inhibitors of Staphylococcus Aureus Adherence to Keratinocytes. PLoS One, 11(7). View this article in WRRO
- Two complementary approaches for intracellular delivery of exogenous enzymes. Scientific Reports, 5, 12444-12444. View this article in WRRO
- Distinct Regions of the Large Extracellular Domain of Tetraspanin CD9 Are Involved in the Control of Human Multinucleated Giant Cell Formation. PLoS ONE, 9(12). View this article in WRRO
- Tetraspanins: gateways for infection.. Infect Disord Drug Targets, 12(1), 4-17.
- A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A.. Science, 334(6057), 821-824. View this article in WRRO
- Cooperative role for tetraspanins in adhesin-mediated attachment of bacterial species to human epithelial cells.. Infect Immun, 79(6), 2241-2249. View this article in WRRO
- The role of tetraspanins in fusion.. Biochem Soc Trans, 39(2), 524-528.
- Regulation of zebrafish hatching by tetraspanin cd63.. PLoS One, 6(5), e19683. View this article in WRRO
- Distinct roles for tetraspanins CD9, CD63 and CD81 in the formation of multinucleated giant cells.. Immunology, 127(2), 237-248.
- Strategies for targeting tetraspanin proteins: potential therapeutic applications in microbial infections.. BioDrugs, 23(6), 341-359. View this article in WRRO
- Characterisation of receptor binding by the chemotaxis inhibitory protein of Staphylococcus aureus and the effects of the host immune response.. Mol Immunol, 44(10), 2507-2517.
- The role of the N-terminal domain of the complement fragment receptor C5L2 in ligand binding.. J Biol Chem, 282(6), 3664-3671.
- Recombinant extracellular domains of tetraspanin proteins are potent inhibitors of the infection of macrophages by human immunodeficiency virus type 1. J VIROL, 80(13), 6487-6496.
- The isolation and characterisation of antiplatelet antibodies. EUR J HAEMATOL, 76(4), 331-338.
- Tetraspanins in viral infections: a fundamental role in viral biology?. J Virol, 79(17), 10839-10851.
- Crystallization of a carbamatase catalytic antibody Fab fragment and its complex with a transition-state analogue.. Acta Crystallogr D Biol Crystallogr, 60(Pt 1), 172-174.
- Structural requirements for the inhibitory action of the CD9 large extracellular domain in sperm/oocyte binding and fusion.. Biochem Biophys Res Commun, 311(1), 208-214.
- High-resolution crystal structure of the Fab-fragments of a family of mouse catalytic antibodies with esterase activity.. J Mol Biol, 332(2), 423-435.
- Interspecies contamination of the KM3 cell line: Implications for CD63 function in melanoma metastasis. INT J CANCER, 105(5), 613-616.
- Turnover-based in vitro selection and evolution of biocatalysts from a fully synthetic antibody library. NAT BIOTECHNOL, 21(6), 679-685.
- The role of somatic mutation in determining the affinity of anti-DNA antibodies.. Clin Exp Immunol, 131(1), 182-189.
- Production of human monoclonal antibodies to an ovarian carcinoma-associated antigen (HPLAP) using phage display. J PATHOL, 198, 19A-19A.
- Direkte Identifizierung von Proteinkatalysatoren mit Phosphatase-Aktivität durch kovalente Bindung an ein Suizid-Substrat. Angewandte Chemie, 114(9), 1528-1528.
- Direct Screening for Phosphatase Activity by Turnover-Based Capture of Protein Catalysts. Angewandte Chemie International Edition, 41(9), 1460-1460.
- Direkte Identifizierung von Proteinkatalysatoren mit Phosphatase-Aktivität durch kovalente Bindung an ein Suizid-Substrat. Angewandte Chemie, 114(5), 801-803.
- Direct screening for phosphatase activity by turnover-based capture of protein catalysts.. Angew Chem Int Ed Engl, 41(5), 775-777.
- Erratum: (Angewandte Chemie - International Edition (2002) 5 (775-777)). Angewandte Chemie - International Edition, 41(9), 1460.
- The preparation and crystallization of Fab fragments of a family of mouse esterolytic catalytic antibodies and their complexes with a transition-state analogue.. Acta Crystallogr D Biol Crystallogr, 57(Pt 8), 1192-1195.
- The identification of endothelial cell autoantigens. J AUTOIMMUN, 15(1), 41-49.
- Antibody cross-linking of human CD9 and the high-affinity immunoglobulin E receptor stimulates secretion from transfected rat basophilic leukaemia cells.. Immunology, 99(4), 546-552.
- A combinatorial phage display library for the generation of specific Fab fragments recognizing human spermatozoa and inhibiting fertilizing capacity in vitro.. Biol Reprod, 59(5), 1180-1186.
- A human monoclonal antiendothelial cell autoantibody uses a VH gene associated with an anti-DNA autoantibody.. Biochem Soc Trans, 25(2), 321S.
- A human monoclonal antiendothelial cell autoantibody uses a V-H gene associated with an anti-DNA autoantibody.. BIOCHEM SOC T, 25(2), S321-S321.
- Antibody catalysis of B(Ac)2 aryl carbamate ester hydrolysis: A highly disfavored chemical process. J AM CHEM SOC, 119(9), 2315-2316.
- A human monoclonal antiendothelial cell autoantibody uses a V-H gene associated an anti-DNA autoantibody. IMMUNOLOGY, 89, BB321-BB321.
- The medical potential of catalytic antibodies. PURE APPL CHEM, 68(11), 2009-2016.
- Analysis of the reactivity of antibodies from the blind panel of the myeloid workshop with hCD63. TISSUE ANTIGENS, 48(4-II), MC505-MC505.
- hCD63 binding by MAb's from the platelet workshop blind panel. TISSUE ANTIGENS, 48(4-II), PL105-PL105.
- Toward antibody-directed ''abzyme'' prodrug therapy, ADAPT: Carbamate prodrug activation by a catalytic antibody and its in vitro application to human tumor cell killing. P NATL ACAD SCI USA, 93(2), 799-803.
- Antibodies against human CD63 activate transfected rat basophilic leukemia (RBL-2H3) cells.. Mol Immunol, 32(17-18), 1339-1344.
- Mutation of glutamate 199 of the human C5a receptor defines a binding site for ligand distinct from the receptor N terminus.. J Biol Chem, 270(28), 16625-16629.
- CHARACTERIZATION OF NUCLEAR TRANSPORT-SYSTEM AND MOLECULES INVOLVED IN NUCLEAR-PROTEIN LOCALIZATION IN HUMAN MONONUCLEAR PHAGOCYTE CELL-LINES. J CELL BIOCHEM, 145-145.
- Multiple signalling pathways in the C5a-induced expression of adhesion receptor Mac-1.. Biochim Biophys Acta, 1221(3), 323-329.
- DIGESTION OF ACTIN WITH GLY-C AND THE LOCALIZATION OF THE EPITOPE FOR THE MONOCLONAL-ANTIBODY NH3. J MUSCLE RES CELL M, 15(2), 196-196.
- STRATEGIES FOR THE PRODUCTION OF CATALYTIC ANTIBODIES USING COMBINATORIAL LIBRARIES. J CELL BIOCHEM, 195-195.
- HUMAN THYROID AUTOANTIBODIES FROM PCOMB3 PHAGE DISPLAY COMBINATORIAL LIBRARIES. J CELL BIOCHEM, 200-200.
- The production of monoclonal antibodies to membrane proteins.. Methods Mol Biol, 27, 65-86.
- Cloning and characterisation of TPO autoantibodies using combinatorial phage display libraries.. Autoimmunity, 17(3), 167-179.
- New strategies for the generation of catalytic antibodies.. Biochem Soc Trans, 21(4), 415S.
- Characterization of a complement-fragment-C5a-stimulated calcium-influx mechanism in U937 monocytic cells.. Biochem J, 295 ( Pt 3), 679-684.
- Production of catalytic antibodies using combinatorial libraries.. Biochem Soc Trans, 21(4), 1096-1098.
- HUMAN MONOCLONAL-ANTIBODIES AGAINST A PLETHORA OF VIRAL PATHOGENS FROM SINGLE COMBINATORIAL LIBRARIES. P NATL ACAD SCI USA, 90(9), 4141-4145.
- Characterization of a monoclonal antibody recognizing a novel leucocyte adhesion molecule.. Biochem Soc Trans, 18(2), 274-275.
- Isoprenaline-induced and constitutive members of a proline-rich protein sub-group from mouse parotid glands studied with monoclonal antibody NAL1.. J Mol Endocrinol, 3(1), 7-14.
- Molecular recognition of antibody (IgG) by cellular Fc receptor (FcRI).. Mol Immunol, 25(11), 1175-1181.
- LOCALIZATION OF THE BINDING-SITE FOR THE HUMAN HIGH-AFFINITY FC RECEPTOR ON IGG. NATURE, 332(6164), 563-564.
- INITIAL CHARACTERIZATION OF AN ANTI-ACTIN MONOCLONAL-ANTIBODY (NH3). BIOCHEM SOC T, 16(2), 163-164.
- Comparison of human monocytes isolated by elutriation and adherence suggests that heterogeneity may reflect a continuum of maturation/activation states.. Immunology, 63(3), 491-498.
- Dibutyryl cyclic AMP stimulation of a monocyte-like cell line, U937: a model for monocyte chemotaxis and Fc receptor-related functions.. Immunology, 63(3), 483-490.
- CHARACTERIZATION OF A MONOCLONAL-ANTIBODY (DA1) WHICH REACTS WITH BONE-MATRIX AND BONE CELL CYTOPLASM. BONE, 8(1), 46-46.
- THE USE OF ANTI-IGG MONOCLONAL-ANTIBODIES IN MAPPING THE MONOCYTE RECEPTOR-SITE ON IGG. MOL IMMUNOL, 23(12), 1365-1372.
- LOCALIZATION OF THE MONOCYTE-BINDING REGION ON HUMAN IMMUNOGLOBULIN-G. MOL IMMUNOL, 23(3), 319-330.
- SUBCLASSES OF IGG ON THE SURFACE OF HUMAN-LYMPHOCYTES - A STUDY WITH MONOCLONAL-ANTIBODIES. CLIN EXP IMMUNOL, 56(1), 167-174.
- IMMUNOGENIC AND ANTIGENIC EPITOPES OF IMMUNOGLOBULINS .2. ANTIGENIC DIFFERENCES BETWEEN SECRETED AND MEMBRANE IGG DEMONSTRATED USING MONOCLONAL-ANTIBODIES. J IMMUNOL, 128(1), 1-6.
- The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future Generations. Toxins, 9(11), 344-344. View this article in WRRO
Conference proceedings papers
- The role of tetraspanin proteins in macrophage uptake of Salmonella bacteria. IMMUNOLOGY, Vol. 131 (pp 80-80)
- Roles for tetraspanin proteins in the fusion of human monocytes to form multinucleated giant cells. IMMUNOLOGY, Vol. 125 (pp 6-7)
- Different ligand-binding mechanisms used by the two C5a receptors, C5L2 and C5aR. MOLECULAR IMMUNOLOGY, Vol. 44(1-3) (pp 237-237)
- Passive and catalytic antibodies and drug delivery. PURE AND APPLIED CHEMISTRY, Vol. 76(5) (pp 983-989)
- Inhibition of sperm-oolemma interactions by the extracellular domains of CD9 and CD81. ANDROLOGY IN THE 21ST CENTURY, SHORT COMMUNICATIONS (pp 565-572)
- Does the CDR3 of the heavy chain determine the specificity of autoantibodies in systemic lupus erythematosus?. JOURNAL OF AUTOIMMUNITY, Vol. 11(5) (pp 477-483)
- A role for CD63 in signal transduction. IMMUNOLOGY, Vol. 89 (pp OM114-OM114)
- Identification of potential ligands for CD63 from random peptide libraries. IMMUNOLOGY, Vol. 89 (pp OM117-OM117)