The Tetraspanin CD81 Is Necessary for Partitioning of Coligated CD19/CD21-B Cell Antigen Receptor Complexes into Signaling-Active Lipid Rafts
Tetraspanins have been hypothesized to facilitate the organization of functional multimolecular membrane complexes. In B cells the tetraspanin CD81 is a component of the CD19/CD21 complex. When coligated to the B cell Ag receptor (BCR), the CD19/CD21 complex significantly enhances BCR signaling in p...
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Veröffentlicht in: | The Journal of immunology (1950) 2004-01, Vol.172 (1), p.370-380 |
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creator | Cherukuri, Anu Shoham, Tsipi Sohn, Hae Won Levy, Shoshana Brooks, Stephen Carter, Robert Pierce, Susan K |
description | Tetraspanins have been hypothesized to facilitate the organization of functional multimolecular membrane complexes. In B cells the tetraspanin CD81 is a component of the CD19/CD21 complex. When coligated to the B cell Ag receptor (BCR), the CD19/CD21 complex significantly enhances BCR signaling in part by prolonging the association of the BCR with signaling-active lipid rafts. In this study CD81 is shown to associate with lipid rafts upon coligation of the BCR and the CD19/CD21 complex. Using B cells from CD81-deficient mice we demonstrate that in the absence of CD81, coligated BCR and CD19/CD21 complexes fail to partition into lipid rafts and enhance BCR signaling from rafts. Furthermore, a chimeric CD19 protein that associates only weakly if at all with CD81 fails to promote the association of coligated BCR with lipid rafts. The requirement for CD81 to promote lipid raft association may define a novel mechanism by which tetraspanins function as molecular facilitators of signaling receptors. |
doi_str_mv | 10.4049/jimmunol.172.1.370 |
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In B cells the tetraspanin CD81 is a component of the CD19/CD21 complex. When coligated to the B cell Ag receptor (BCR), the CD19/CD21 complex significantly enhances BCR signaling in part by prolonging the association of the BCR with signaling-active lipid rafts. In this study CD81 is shown to associate with lipid rafts upon coligation of the BCR and the CD19/CD21 complex. Using B cells from CD81-deficient mice we demonstrate that in the absence of CD81, coligated BCR and CD19/CD21 complexes fail to partition into lipid rafts and enhance BCR signaling from rafts. Furthermore, a chimeric CD19 protein that associates only weakly if at all with CD81 fails to promote the association of coligated BCR with lipid rafts. 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In B cells the tetraspanin CD81 is a component of the CD19/CD21 complex. When coligated to the B cell Ag receptor (BCR), the CD19/CD21 complex significantly enhances BCR signaling in part by prolonging the association of the BCR with signaling-active lipid rafts. In this study CD81 is shown to associate with lipid rafts upon coligation of the BCR and the CD19/CD21 complex. Using B cells from CD81-deficient mice we demonstrate that in the absence of CD81, coligated BCR and CD19/CD21 complexes fail to partition into lipid rafts and enhance BCR signaling from rafts. Furthermore, a chimeric CD19 protein that associates only weakly if at all with CD81 fails to promote the association of coligated BCR with lipid rafts. The requirement for CD81 to promote lipid raft association may define a novel mechanism by which tetraspanins function as molecular facilitators of signaling receptors.</description><subject>Adjuvants, Immunologic - physiology</subject><subject>Animals</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - physiology</subject><subject>Antigens, CD19 - metabolism</subject><subject>Antigens, CD19 - physiology</subject><subject>B-Lymphocyte Subsets - immunology</subject><subject>B-Lymphocyte Subsets - metabolism</subject><subject>CD81 antigen</subject><subject>Cell Line, Transformed</subject><subject>Down-Regulation - genetics</subject><subject>Down-Regulation - immunology</subject><subject>Female</subject><subject>Ligands</subject><subject>lipid rafts</subject><subject>Male</subject><subject>Membrane Microdomains - genetics</subject><subject>Membrane Microdomains - immunology</subject><subject>Membrane Microdomains - metabolism</subject><subject>Membrane Proteins - deficiency</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - physiology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred CBA</subject><subject>Mice, Transgenic</subject><subject>Nerve Tissue Proteins - physiology</subject><subject>Receptors, Antigen, B-Cell - metabolism</subject><subject>Receptors, Antigen, B-Cell - physiology</subject><subject>Receptors, Complement 3d - metabolism</subject><subject>Receptors, Complement 3d - physiology</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Recombinant Fusion Proteins - physiology</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - immunology</subject><subject>Tetraspanin 28</subject><subject>Tetraspanins</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAURS0EotPCD7BAXrHL9NlxnGQ5pEArjQCVYW05jp1x5cTB9nTgI_hnjDpolkiW3ubc86x3EXpDYM2AtdcPdpoOs3drUtM1WZc1PEMrUlVQcA78OVoBUFqQmtcX6DLGBwDgQNlLdEEYb5qSVSv0e7fXeKdTkHGRs51xd9MQfBfxZ610jDL8wsYH_FWGZJP1mRixN7jzzo4y6SHzpL3ubigp3uNOO4c3c7KjnvF9FiwpZzs_LU7_1BHbOXn8zY6zdNlTbFSyjxpv7WIHfC9Niq_QCyNd1K9P8wp9__hh190W2y-f7rrNtlAMqlTosoIBCJEyv4r2ZigH6JXUIE1lOJBGUcVULWtWl0ZyaQw0Ax36lkLfl315hd49eZfgfxx0TGKyUeXfy1n7QxRNvlRD2-q_IGkpZSVvMkifQBV8jEEbsQQ75fMJAuJvW-JfWyK3JYjIbeXQ25P90E96OEdO9ZzX7-24P9qgRZykcxkn4ng8nk1_ACjfoKk</recordid><startdate>20040101</startdate><enddate>20040101</enddate><creator>Cherukuri, Anu</creator><creator>Shoham, Tsipi</creator><creator>Sohn, Hae Won</creator><creator>Levy, Shoshana</creator><creator>Brooks, Stephen</creator><creator>Carter, Robert</creator><creator>Pierce, Susan K</creator><general>Am Assoc Immnol</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20040101</creationdate><title>The Tetraspanin CD81 Is Necessary for Partitioning of Coligated CD19/CD21-B Cell Antigen Receptor Complexes into Signaling-Active Lipid Rafts</title><author>Cherukuri, Anu ; Shoham, Tsipi ; Sohn, Hae Won ; Levy, Shoshana ; Brooks, Stephen ; Carter, Robert ; Pierce, Susan K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c405t-e350d011aa1aa52bfd3d0bcae0af5f6018c2c4c7a7473fa6aff08d2db920bb3b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adjuvants, Immunologic - physiology</topic><topic>Animals</topic><topic>Antigens, CD - genetics</topic><topic>Antigens, CD - physiology</topic><topic>Antigens, CD19 - metabolism</topic><topic>Antigens, CD19 - physiology</topic><topic>B-Lymphocyte Subsets - immunology</topic><topic>B-Lymphocyte Subsets - metabolism</topic><topic>CD81 antigen</topic><topic>Cell Line, Transformed</topic><topic>Down-Regulation - genetics</topic><topic>Down-Regulation - immunology</topic><topic>Female</topic><topic>Ligands</topic><topic>lipid rafts</topic><topic>Male</topic><topic>Membrane Microdomains - genetics</topic><topic>Membrane Microdomains - immunology</topic><topic>Membrane Microdomains - metabolism</topic><topic>Membrane Proteins - deficiency</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - physiology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred CBA</topic><topic>Mice, Transgenic</topic><topic>Nerve Tissue Proteins - physiology</topic><topic>Receptors, Antigen, B-Cell - metabolism</topic><topic>Receptors, Antigen, B-Cell - physiology</topic><topic>Receptors, Complement 3d - metabolism</topic><topic>Receptors, Complement 3d - physiology</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Recombinant Fusion Proteins - physiology</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - immunology</topic><topic>Tetraspanin 28</topic><topic>Tetraspanins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cherukuri, Anu</creatorcontrib><creatorcontrib>Shoham, Tsipi</creatorcontrib><creatorcontrib>Sohn, Hae Won</creatorcontrib><creatorcontrib>Levy, Shoshana</creatorcontrib><creatorcontrib>Brooks, Stephen</creatorcontrib><creatorcontrib>Carter, Robert</creatorcontrib><creatorcontrib>Pierce, Susan K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cherukuri, Anu</au><au>Shoham, Tsipi</au><au>Sohn, Hae Won</au><au>Levy, Shoshana</au><au>Brooks, Stephen</au><au>Carter, Robert</au><au>Pierce, Susan K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Tetraspanin CD81 Is Necessary for Partitioning of Coligated CD19/CD21-B Cell Antigen Receptor Complexes into Signaling-Active Lipid Rafts</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2004-01-01</date><risdate>2004</risdate><volume>172</volume><issue>1</issue><spage>370</spage><epage>380</epage><pages>370-380</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Tetraspanins have been hypothesized to facilitate the organization of functional multimolecular membrane complexes. In B cells the tetraspanin CD81 is a component of the CD19/CD21 complex. When coligated to the B cell Ag receptor (BCR), the CD19/CD21 complex significantly enhances BCR signaling in part by prolonging the association of the BCR with signaling-active lipid rafts. In this study CD81 is shown to associate with lipid rafts upon coligation of the BCR and the CD19/CD21 complex. Using B cells from CD81-deficient mice we demonstrate that in the absence of CD81, coligated BCR and CD19/CD21 complexes fail to partition into lipid rafts and enhance BCR signaling from rafts. Furthermore, a chimeric CD19 protein that associates only weakly if at all with CD81 fails to promote the association of coligated BCR with lipid rafts. The requirement for CD81 to promote lipid raft association may define a novel mechanism by which tetraspanins function as molecular facilitators of signaling receptors.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>14688345</pmid><doi>10.4049/jimmunol.172.1.370</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adjuvants, Immunologic - physiology Animals Antigens, CD - genetics Antigens, CD - physiology Antigens, CD19 - metabolism Antigens, CD19 - physiology B-Lymphocyte Subsets - immunology B-Lymphocyte Subsets - metabolism CD81 antigen Cell Line, Transformed Down-Regulation - genetics Down-Regulation - immunology Female Ligands lipid rafts Male Membrane Microdomains - genetics Membrane Microdomains - immunology Membrane Microdomains - metabolism Membrane Proteins - deficiency Membrane Proteins - genetics Membrane Proteins - physiology Mice Mice, Inbred BALB C Mice, Inbred CBA Mice, Transgenic Nerve Tissue Proteins - physiology Receptors, Antigen, B-Cell - metabolism Receptors, Antigen, B-Cell - physiology Receptors, Complement 3d - metabolism Receptors, Complement 3d - physiology Recombinant Fusion Proteins - metabolism Recombinant Fusion Proteins - physiology Signal Transduction - genetics Signal Transduction - immunology Tetraspanin 28 Tetraspanins |
title | The Tetraspanin CD81 Is Necessary for Partitioning of Coligated CD19/CD21-B Cell Antigen Receptor Complexes into Signaling-Active Lipid Rafts |
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