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Erschienen in: Cancer Immunology, Immunotherapy 3/2004

01.03.2004 | Review

Tetraspanins connect several types of Ig proteins: IgM is a novel component of the tetraspanin web on B-lymphoid cells

verfasst von: François Le Naour, Stéphanie Charrin, Valérie Labas, Jean-Pierre Le Caer, Claude Boucheix, Eric Rubinstein

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 3/2004

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Abstract

The tetraspanins form a family of about 30 molecules mainly expressed on the cell surface. They have been reported to be involved in many physiological or pathological processes, such as fertilization, immune response, development of the nervous system, and metastasis, as well as in infectious diseases (HCV, malaria, etc.). The tetraspanins may play a role as “organizers” of multimolecular complexes on the cell surface associating numerous proteins, the “tetraspanin web.” To better define the composition of the tetraspanin web, its characterization has been recently performed using mass spectrometry and proteomics. We report the proteomic analysis of tetraspanin complexes on B-lymphoid cells. Immunoprecipitation experiments were performed using mAbs directed against the tetraspanin CD9, and associated molecules were identified by MALDI-TOF (matrix assisted laser desorption ionization time of flight) mass spectrometry. This led to the identification of IgM as a novel component of the complexes. Thus, tetraspanins may connect several types of proteins with Ig domains, including HLA-DR, EWI-2, and IgM, that may play a role in immune responses.
Literatur
1.
Zurück zum Zitat Boucheix C, Rubinstein E (2001) Tetraspanins. Cell Mol Life Sci 58:1189–1205PubMed Boucheix C, Rubinstein E (2001) Tetraspanins. Cell Mol Life Sci 58:1189–1205PubMed
2.
Zurück zum Zitat Charrin S, Le Naour F, Oualid M, Billard M, Faure G, Hanash SM, Boucheix C, Rubinstein E (2001) The major CD9 and CD81 molecular partner: Identification and characterization of the complexes. J Biol Chem 276:14329–14337PubMed Charrin S, Le Naour F, Oualid M, Billard M, Faure G, Hanash SM, Boucheix C, Rubinstein E (2001) The major CD9 and CD81 molecular partner: Identification and characterization of the complexes. J Biol Chem 276:14329–14337PubMed
3.
Zurück zum Zitat Charrin S, Manie S, Oualid M, Billard M, Boucheix C, Rubinstein E (2002) Differential stability of tetraspanin/tetraspanin interactions: role of palmitoylation. FEBS Lett 516:139–144CrossRefPubMed Charrin S, Manie S, Oualid M, Billard M, Boucheix C, Rubinstein E (2002) Differential stability of tetraspanin/tetraspanin interactions: role of palmitoylation. FEBS Lett 516:139–144CrossRefPubMed
4.
Zurück zum Zitat Charrin S, Manie S, Billard M, Ashman L, Gerlier D, Boucheix C, Rubinstein E (2003) Multiple levels of interactions within the tetraspanin web. Biochem Biophys Res Commun 304:107–112CrossRefPubMed Charrin S, Manie S, Billard M, Ashman L, Gerlier D, Boucheix C, Rubinstein E (2003) Multiple levels of interactions within the tetraspanin web. Biochem Biophys Res Commun 304:107–112CrossRefPubMed
5.
Zurück zum Zitat Charrin S, Le Naour F, Billard M, Labas V, Le Caer JP, Emile JF, Petit MA, Boucheix C, Rubinstein E (2003) EWI-2 is a new component of the tetraspanin web in hepatocytes and lymphoid cells. Biochem. J 373:409–421 Charrin S, Le Naour F, Billard M, Labas V, Le Caer JP, Emile JF, Petit MA, Boucheix C, Rubinstein E (2003) EWI-2 is a new component of the tetraspanin web in hepatocytes and lymphoid cells. Biochem. J 373:409–421
6.
Zurück zum Zitat Charrin S, Manie S, Thiele C, Billard M, Gerlier D, Boucheix C, Rubinstein E (2003) A physical and functional link between cholesterol and tetraspanins. Eur J Immunol 33:2479–2489CrossRefPubMed Charrin S, Manie S, Thiele C, Billard M, Gerlier D, Boucheix C, Rubinstein E (2003) A physical and functional link between cholesterol and tetraspanins. Eur J Immunol 33:2479–2489CrossRefPubMed
7.
Zurück zum Zitat Claas C, Stipp CS, Hemler ME (2001) Evaluation of prototype transmembrane 4 superfamily protein complexes and their relation to lipid rafts. J Biol Chem 276:7974–7984CrossRefPubMed Claas C, Stipp CS, Hemler ME (2001) Evaluation of prototype transmembrane 4 superfamily protein complexes and their relation to lipid rafts. J Biol Chem 276:7974–7984CrossRefPubMed
8.
Zurück zum Zitat Clark KL, Zeng Z, Langford AL, Bowen SM, Todd SC (2001) PGRL is a major CD81-associated protein on lymphocytes and distinguishes a new family of cell surface proteins. J Immunol 167:5115–5121PubMed Clark KL, Zeng Z, Langford AL, Bowen SM, Todd SC (2001) PGRL is a major CD81-associated protein on lymphocytes and distinguishes a new family of cell surface proteins. J Immunol 167:5115–5121PubMed
9.
Zurück zum Zitat Deng J, Dekruyff RH, Freeman GJ, Umetsu DT, Levy S (2002) Critical role of CD81 in cognate T-B cell interactions leading to Th2 responses. Int Immunol 14:513–523CrossRefPubMed Deng J, Dekruyff RH, Freeman GJ, Umetsu DT, Levy S (2002) Critical role of CD81 in cognate T-B cell interactions leading to Th2 responses. Int Immunol 14:513–523CrossRefPubMed
10.
Zurück zum Zitat Engering A, Pieters J (2001) Association of distinct tetraspanins with MHC class II molecules at different subcellular locations in human immature dendritic cells. Int Immunol 13:127–134CrossRefPubMed Engering A, Pieters J (2001) Association of distinct tetraspanins with MHC class II molecules at different subcellular locations in human immature dendritic cells. Int Immunol 13:127–134CrossRefPubMed
11.
Zurück zum Zitat Engering A, Kuhn L, Fluitsma D, Hoefsmit E, Pieters J (2003) Differential post-translational modification of CD63 molecules during maturation of human dendritic cells. Eur J Biochem 270:2412–2420CrossRefPubMed Engering A, Kuhn L, Fluitsma D, Hoefsmit E, Pieters J (2003) Differential post-translational modification of CD63 molecules during maturation of human dendritic cells. Eur J Biochem 270:2412–2420CrossRefPubMed
12.
Zurück zum Zitat Escola JM, Kleijmeer MJ, Stoorvogel W, Griffith JM, Yoshie O, Geuze HJ (1998) Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem 273:20121–20127CrossRefPubMed Escola JM, Kleijmeer MJ, Stoorvogel W, Griffith JM, Yoshie O, Geuze HJ (1998) Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem 273:20121–20127CrossRefPubMed
13.
Zurück zum Zitat Fritzsching B, Schwer B, Kartenbeck J, Pedal A, Horejsi V, Ott M (2002) Release and intercellular transfer of cell surface CD81 via microparticles. J Immunol 169:5531–5537PubMed Fritzsching B, Schwer B, Kartenbeck J, Pedal A, Horejsi V, Ott M (2002) Release and intercellular transfer of cell surface CD81 via microparticles. J Immunol 169:5531–5537PubMed
14.
Zurück zum Zitat Knobeloch KP, Wright MD, Ochsenbein AF, Liesenfeld O, Lohler J, Zinkernagel RM, Horak I, Orinska Z (2000) Targeted inactivation of the tetraspanin CD37 impairs T-cell-dependent B-cell response under suboptimal costimulatory conditions. Mol Cell Biol 20:5363–5369CrossRefPubMed Knobeloch KP, Wright MD, Ochsenbein AF, Liesenfeld O, Lohler J, Zinkernagel RM, Horak I, Orinska Z (2000) Targeted inactivation of the tetraspanin CD37 impairs T-cell-dependent B-cell response under suboptimal costimulatory conditions. Mol Cell Biol 20:5363–5369CrossRefPubMed
15.
Zurück zum Zitat Kropshofer H, Spindeldreher S, Rohn TA, Platania N, Grygar C, Daniel N, Wolpl A, Langen H, Horejsi V, Vogt AB (2002) Tetraspan microdomains distinct from lipid rafts enrich select peptide-MHC class II complexes. Nat Immunol 3:61–68CrossRefPubMed Kropshofer H, Spindeldreher S, Rohn TA, Platania N, Grygar C, Daniel N, Wolpl A, Langen H, Horejsi V, Vogt AB (2002) Tetraspan microdomains distinct from lipid rafts enrich select peptide-MHC class II complexes. Nat Immunol 3:61–68CrossRefPubMed
16.
Zurück zum Zitat Lagaudrière-Gesbert C, Le Naour F, Lebel-Binay S, Billard M, Lemichez E, Boquet P, Boucheix C, Conjeaud H, Rubinstein E (1997) Functional analysis of 4 tetraspans, CD9, CD81, CD53 and CD82, suggests a common role in costimulation, cell adhesion and migration: only CD9 upregulates HB-EGF activity. Cellular Immunol 182:105–112CrossRef Lagaudrière-Gesbert C, Le Naour F, Lebel-Binay S, Billard M, Lemichez E, Boquet P, Boucheix C, Conjeaud H, Rubinstein E (1997) Functional analysis of 4 tetraspans, CD9, CD81, CD53 and CD82, suggests a common role in costimulation, cell adhesion and migration: only CD9 upregulates HB-EGF activity. Cellular Immunol 182:105–112CrossRef
17.
Zurück zum Zitat Lamparski HG, Metha-Damani A, Yao JY, Patel S, Hsu DH, Ruegg C, Le Pecq JB (2002) Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Methods 270:211–226PubMed Lamparski HG, Metha-Damani A, Yao JY, Patel S, Hsu DH, Ruegg C, Le Pecq JB (2002) Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Methods 270:211–226PubMed
18.
Zurück zum Zitat Levy S, Todd SC, Maecker HT (1998) CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system. Annu Rev Immunol 16:89–109CrossRefPubMed Levy S, Todd SC, Maecker HT (1998) CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system. Annu Rev Immunol 16:89–109CrossRefPubMed
19.
Zurück zum Zitat Maecker HT (2003) Human CD81 directly enhances Th1 and Th2 cell activation, but preferentially induces proliferation of Th2 cells upon long-term stimulation. BMC Immunol 4:1CrossRefPubMed Maecker HT (2003) Human CD81 directly enhances Th1 and Th2 cell activation, but preferentially induces proliferation of Th2 cells upon long-term stimulation. BMC Immunol 4:1CrossRefPubMed
20.
Zurück zum Zitat Maecker HT, Levy S (1997) Normal lymphocyte development but delayed humoral immune response in CD81-null mice. J Exp Med 185:1505–1510CrossRefPubMed Maecker HT, Levy S (1997) Normal lymphocyte development but delayed humoral immune response in CD81-null mice. J Exp Med 185:1505–1510CrossRefPubMed
21.
Zurück zum Zitat Mittelbrunn M, Yanez-Mo M, Sancho D, Ursa A, Sanchez-Madrid F (2002) Cutting edge: dynamic redistribution of tetraspanin CD81 at the central zone of the immune synapse in both T lymphocytes and APC. J Immunol 169:6691–6695PubMed Mittelbrunn M, Yanez-Mo M, Sancho D, Ursa A, Sanchez-Madrid F (2002) Cutting edge: dynamic redistribution of tetraspanin CD81 at the central zone of the immune synapse in both T lymphocytes and APC. J Immunol 169:6691–6695PubMed
22.
Zurück zum Zitat Miyazaki T, Muller U, Campbell KS (1997) Normal development but differentially altered proliferative responses of lymphocytes in mice lacking CD81. EMBO J 16:4217–4225CrossRefPubMed Miyazaki T, Muller U, Campbell KS (1997) Normal development but differentially altered proliferative responses of lymphocytes in mice lacking CD81. EMBO J 16:4217–4225CrossRefPubMed
23.
Zurück zum Zitat Oren R, Takahashi S, Doss C, Levy R, Levy S (1990) TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins. Mol Cell Biol 10:4007–4015PubMed Oren R, Takahashi S, Doss C, Levy R, Levy S (1990) TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins. Mol Cell Biol 10:4007–4015PubMed
24.
Zurück zum Zitat Rubinstein E, Le Naour F, Lagaudrière-Gesbert C, Billard M, Conjeaud H, Boucheix C (1996) CD9, CD63, CD81 and CD82 are components of a surface tetraspan network connected to HLA-DR and VLA integrins. Eur J Immunol 26:2657–2665PubMed Rubinstein E, Le Naour F, Lagaudrière-Gesbert C, Billard M, Conjeaud H, Boucheix C (1996) CD9, CD63, CD81 and CD82 are components of a surface tetraspan network connected to HLA-DR and VLA integrins. Eur J Immunol 26:2657–2665PubMed
25.
Zurück zum Zitat Serru V, Le Naour F, Billard M, Azorsa D, O, Lanza F, Boucheix C, Rubinstein E (1999) Selective tetraspan-integrin complexes (CD81/α4β1, CD151/α3β1, CD151/α6β1) under conditions disrupting tetraspan interactions. Biochem J 340:103–111CrossRefPubMed Serru V, Le Naour F, Billard M, Azorsa D, O, Lanza F, Boucheix C, Rubinstein E (1999) Selective tetraspan-integrin complexes (CD81/α4β1, CD151/α3β1, CD151/α6β1) under conditions disrupting tetraspan interactions. Biochem J 340:103–111CrossRefPubMed
26.
Zurück zum Zitat Stipp CS, Orlicky D, Hemler ME (2001) FPRP, a major, highly stoichiometric, highly specific CD81- and CD9-associated protein. J Biol Chem 276:4853–4862CrossRefPubMed Stipp CS, Orlicky D, Hemler ME (2001) FPRP, a major, highly stoichiometric, highly specific CD81- and CD9-associated protein. J Biol Chem 276:4853–4862CrossRefPubMed
27.
Zurück zum Zitat Stipp CS, Kolesnikova TV, Hemler ME (2001) EWI-2 is a major CD9 and CD81 partner and member of a novel Ig protein subfamily. J Biol Chem 276:40545–40554CrossRefPubMed Stipp CS, Kolesnikova TV, Hemler ME (2001) EWI-2 is a major CD9 and CD81 partner and member of a novel Ig protein subfamily. J Biol Chem 276:40545–40554CrossRefPubMed
28.
Zurück zum Zitat Stipp CS, Kolesnikova TV, Hemler ME (2003) Functional domains in tetraspanin proteins.Trends Biochem Sci 28:106–112CrossRefPubMed Stipp CS, Kolesnikova TV, Hemler ME (2003) Functional domains in tetraspanin proteins.Trends Biochem Sci 28:106–112CrossRefPubMed
29.
Zurück zum Zitat Thery C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, Raposo G, Amigorena S (1999) Molecular characterization of dendritic cell-derived exosomes: selective accumulation of the heat shock protein hsc73. J Cell Biol 147:599–610CrossRefPubMed Thery C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, Raposo G, Amigorena S (1999) Molecular characterization of dendritic cell-derived exosomes: selective accumulation of the heat shock protein hsc73. J Cell Biol 147:599–610CrossRefPubMed
30.
Zurück zum Zitat Tsitsikov EN, Gutierrez-Ramos JC, Geha RS (1997) Impaired CD19 expression and signaling, enhanced antibody response to type II T independent antigen and reduction of B-1 cells in CD81-deficient mice. Proc Natl Acad Sci U S A 94:10844–10849CrossRefPubMed Tsitsikov EN, Gutierrez-Ramos JC, Geha RS (1997) Impaired CD19 expression and signaling, enhanced antibody response to type II T independent antigen and reduction of B-1 cells in CD81-deficient mice. Proc Natl Acad Sci U S A 94:10844–10849CrossRefPubMed
31.
Zurück zum Zitat Vogt AB, Spindeldreher S, Kropshofer H (2002) Clustering of MHC-peptide complexes prior to their engagement in the immunological synapse: lipid raft and tetraspan microdomains. Immunol Rev 189:136–151CrossRefPubMed Vogt AB, Spindeldreher S, Kropshofer H (2002) Clustering of MHC-peptide complexes prior to their engagement in the immunological synapse: lipid raft and tetraspan microdomains. Immunol Rev 189:136–151CrossRefPubMed
32.
Zurück zum Zitat Wubbolts R, Leckie RS, Veenhuizen PT, Schwarzmann G, Mobius W, Hoernschemeyer J, Slot JW, Geuze HJ, Stoorvogel W (2003) Proteomic and biochemical analyses of human B cell-derived exosomes: potential implications for their function and multivesicular body formation. J Biol Chem 278:10963–10972CrossRefPubMed Wubbolts R, Leckie RS, Veenhuizen PT, Schwarzmann G, Mobius W, Hoernschemeyer J, Slot JW, Geuze HJ, Stoorvogel W (2003) Proteomic and biochemical analyses of human B cell-derived exosomes: potential implications for their function and multivesicular body formation. J Biol Chem 278:10963–10972CrossRefPubMed
33.
Zurück zum Zitat Yang X, Claas C, Kraeft SK, Chen LB, Wang Z, Kreidberg JA, Hemler ME (2002) Palmitoylation of tetraspanin proteins: modulation of CD151 lateral interactions, subcellular distribution, and integrin-dependent cell morphology. Mol Biol Cell 13:767–781CrossRefPubMed Yang X, Claas C, Kraeft SK, Chen LB, Wang Z, Kreidberg JA, Hemler ME (2002) Palmitoylation of tetraspanin proteins: modulation of CD151 lateral interactions, subcellular distribution, and integrin-dependent cell morphology. Mol Biol Cell 13:767–781CrossRefPubMed
34.
Zurück zum Zitat Zhang XA, Lane WS, Charrin S, Rubinstein E, Liu L (2003) EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells. Cancer Res 200363:2665–2674 Zhang XA, Lane WS, Charrin S, Rubinstein E, Liu L (2003) EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells. Cancer Res 200363:2665–2674
35.
Zurück zum Zitat Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, Ricciardi-Castagnoli P, Raposo G, Amigorena S (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med 4:594–600PubMed Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, Ricciardi-Castagnoli P, Raposo G, Amigorena S (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med 4:594–600PubMed
Metadaten
Titel
Tetraspanins connect several types of Ig proteins: IgM is a novel component of the tetraspanin web on B-lymphoid cells
verfasst von
François Le Naour
Stéphanie Charrin
Valérie Labas
Jean-Pierre Le Caer
Claude Boucheix
Eric Rubinstein
Publikationsdatum
01.03.2004
Verlag
Springer-Verlag
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 3/2004
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-003-0477-5

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