Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance
Membrane microdomains (lipid rafts) are now recognized as critical for proper compartmentalization of insulin signaling. We previously demonstrated that, in adipocytes in a state of TNFα-induced insulin resistance, the inhibition of insulin metabolic signaling and the elimination of insulin receptor...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2007-08, Vol.104 (34), p.13678-13683 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 13683 |
|---|---|
| container_issue | 34 |
| container_start_page | 13678 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 104 |
| creator | Kabayama, Kazuya Sato, Takashige Saito, Kumiko Loberto, Nicoletta Prinetti, Alessandro Sonnino, Sandro Kinjo, Masataka Igarashi, Yasuyuki Inokuchi, Jin-ichi |
| description | Membrane microdomains (lipid rafts) are now recognized as critical for proper compartmentalization of insulin signaling. We previously demonstrated that, in adipocytes in a state of TNFα-induced insulin resistance, the inhibition of insulin metabolic signaling and the elimination of insulin receptors (IR) from the caveolae microdomains were associated with an accumulation of the ganglioside GM3. To gain insight into molecular mechanisms behind interactions of IR, caveolin-1 (Cav1), and GM3 in adipocytes, we have performed immunoprecipitations, cross-linking studies of IR and GM3, and live cell studies using total internal reflection fluorescence microscopy and fluorescence recovery after photobleaching techniques. We found that (i) IR form complexes with Cav1 and GM3 independently; (ii) in GM3-enriched membranes the mobility of IR is increased by dissociation of the IR-Cav1 interaction; and (iii) the lysine residue localized just above the transmembrane domain of the IR β-subunit is essential for the interaction of IR with GM3. Because insulin metabolic signal transduction in adipocytes is known to be critically dependent on caveolae, we propose a pathological feature of insulin resistance in adipocytes caused by dissociation of the IR-Cav1 complex by the interactions of IR with GM3 in microdomains. |
| doi_str_mv | 10.1073/pnas.0703650104 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_pnas_</sourceid><recordid>TN_cdi_pnas_primary_104_34_13678_fulltext</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>25436550</jstor_id><sourcerecordid>25436550</sourcerecordid><originalsourceid>FETCH-LOGICAL-c589t-2426f97039c5ebeb1b6d91c3834c5fa57d5ac325c7a6fcb078e181b409e91c303</originalsourceid><addsrcrecordid>eNqFkUFv1DAQhS0EokvhzAmwOCBxSDuO7cS-VEIFClIRB-jZchxn61XWTm2nav89DrvqAhdOlma-9zTPD6GXBE4ItPR08jqdQAu04UCAPUIrApJUDZPwGK0A6rYSrGZH6FlKGwCQXMBTdETaRsqGtCt089GlFIzT2QWPw4DztcXOp3l0Hkdr7JRDxNr32OhbG8q0ItiE7TTaO9zd47X269GF5HqLL77RIv3tkLLOdrE7WCVXht7Y5-jJoMdkX-zfY3T1-dPP8y_V5feLr-cfLivDhcxVzepmkCWZNNx2tiNd00tiqKDM8EHztufa0JqbVjeD6aAVlgjSMZB2wYAeo7Od7zR3W9sb63PUo5qi2-p4r4J26u-Nd9dqHW4VkUxSVheDd3uDGG5mm7LaumTsOGpvw5xUIwopqCzg23_ATZijL-FUDYTRWoqmQKc7yMSQUrTDwyUE1NKlWrpUhy6L4vWfAQ78vrwCvN8Di_JgxxRlitCmFWqYxzHbu1xY_B-2IK92yCaVzh-YmrNyEV8-9M1uP-ig9Dq6pK5-lIAUQAAwIegvyyvHdA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>201432986</pqid></control><display><type>article</type><title>Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance</title><source>MEDLINE</source><source>JSTOR Archive Collection A-Z Listing</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Kabayama, Kazuya ; Sato, Takashige ; Saito, Kumiko ; Loberto, Nicoletta ; Prinetti, Alessandro ; Sonnino, Sandro ; Kinjo, Masataka ; Igarashi, Yasuyuki ; Inokuchi, Jin-ichi</creator><creatorcontrib>Kabayama, Kazuya ; Sato, Takashige ; Saito, Kumiko ; Loberto, Nicoletta ; Prinetti, Alessandro ; Sonnino, Sandro ; Kinjo, Masataka ; Igarashi, Yasuyuki ; Inokuchi, Jin-ichi</creatorcontrib><description>Membrane microdomains (lipid rafts) are now recognized as critical for proper compartmentalization of insulin signaling. We previously demonstrated that, in adipocytes in a state of TNFα-induced insulin resistance, the inhibition of insulin metabolic signaling and the elimination of insulin receptors (IR) from the caveolae microdomains were associated with an accumulation of the ganglioside GM3. To gain insight into molecular mechanisms behind interactions of IR, caveolin-1 (Cav1), and GM3 in adipocytes, we have performed immunoprecipitations, cross-linking studies of IR and GM3, and live cell studies using total internal reflection fluorescence microscopy and fluorescence recovery after photobleaching techniques. We found that (i) IR form complexes with Cav1 and GM3 independently; (ii) in GM3-enriched membranes the mobility of IR is increased by dissociation of the IR-Cav1 interaction; and (iii) the lysine residue localized just above the transmembrane domain of the IR β-subunit is essential for the interaction of IR with GM3. Because insulin metabolic signal transduction in adipocytes is known to be critically dependent on caveolae, we propose a pathological feature of insulin resistance in adipocytes caused by dissociation of the IR-Cav1 complex by the interactions of IR with GM3 in microdomains.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0703650104</identifier><identifier>PMID: 17699617</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>3T3-L1 Cells ; Adipocytes ; Animals ; Antibodies ; Biological Sciences ; Caveolae ; Caveolin 1 - genetics ; Caveolin 1 - metabolism ; Cell membranes ; Cell Survival ; Fluorescence ; G(M3) Ganglioside - metabolism ; Gangliosides ; HEK293 cells ; Insulin ; Insulin Resistance ; Lipids ; Lysine - genetics ; Lysine - metabolism ; Mice ; Protein Binding ; Receptor, Insulin - metabolism ; Signal Transduction ; Spectrum analysis ; T cell receptors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2007-08, Vol.104 (34), p.13678-13683</ispartof><rights>Copyright 2007 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Aug 21, 2007</rights><rights>2007 by The National Academy of Sciences of the USA 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c589t-2426f97039c5ebeb1b6d91c3834c5fa57d5ac325c7a6fcb078e181b409e91c303</citedby><cites>FETCH-LOGICAL-c589t-2426f97039c5ebeb1b6d91c3834c5fa57d5ac325c7a6fcb078e181b409e91c303</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/104/34.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25436550$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25436550$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17699617$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kabayama, Kazuya</creatorcontrib><creatorcontrib>Sato, Takashige</creatorcontrib><creatorcontrib>Saito, Kumiko</creatorcontrib><creatorcontrib>Loberto, Nicoletta</creatorcontrib><creatorcontrib>Prinetti, Alessandro</creatorcontrib><creatorcontrib>Sonnino, Sandro</creatorcontrib><creatorcontrib>Kinjo, Masataka</creatorcontrib><creatorcontrib>Igarashi, Yasuyuki</creatorcontrib><creatorcontrib>Inokuchi, Jin-ichi</creatorcontrib><title>Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Membrane microdomains (lipid rafts) are now recognized as critical for proper compartmentalization of insulin signaling. We previously demonstrated that, in adipocytes in a state of TNFα-induced insulin resistance, the inhibition of insulin metabolic signaling and the elimination of insulin receptors (IR) from the caveolae microdomains were associated with an accumulation of the ganglioside GM3. To gain insight into molecular mechanisms behind interactions of IR, caveolin-1 (Cav1), and GM3 in adipocytes, we have performed immunoprecipitations, cross-linking studies of IR and GM3, and live cell studies using total internal reflection fluorescence microscopy and fluorescence recovery after photobleaching techniques. We found that (i) IR form complexes with Cav1 and GM3 independently; (ii) in GM3-enriched membranes the mobility of IR is increased by dissociation of the IR-Cav1 interaction; and (iii) the lysine residue localized just above the transmembrane domain of the IR β-subunit is essential for the interaction of IR with GM3. Because insulin metabolic signal transduction in adipocytes is known to be critically dependent on caveolae, we propose a pathological feature of insulin resistance in adipocytes caused by dissociation of the IR-Cav1 complex by the interactions of IR with GM3 in microdomains.</description><subject>3T3-L1 Cells</subject><subject>Adipocytes</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Biological Sciences</subject><subject>Caveolae</subject><subject>Caveolin 1 - genetics</subject><subject>Caveolin 1 - metabolism</subject><subject>Cell membranes</subject><subject>Cell Survival</subject><subject>Fluorescence</subject><subject>G(M3) Ganglioside - metabolism</subject><subject>Gangliosides</subject><subject>HEK293 cells</subject><subject>Insulin</subject><subject>Insulin Resistance</subject><subject>Lipids</subject><subject>Lysine - genetics</subject><subject>Lysine - metabolism</subject><subject>Mice</subject><subject>Protein Binding</subject><subject>Receptor, Insulin - metabolism</subject><subject>Signal Transduction</subject><subject>Spectrum analysis</subject><subject>T cell receptors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS0EokvhzAmwOCBxSDuO7cS-VEIFClIRB-jZchxn61XWTm2nav89DrvqAhdOlma-9zTPD6GXBE4ItPR08jqdQAu04UCAPUIrApJUDZPwGK0A6rYSrGZH6FlKGwCQXMBTdETaRsqGtCt089GlFIzT2QWPw4DztcXOp3l0Hkdr7JRDxNr32OhbG8q0ItiE7TTaO9zd47X269GF5HqLL77RIv3tkLLOdrE7WCVXht7Y5-jJoMdkX-zfY3T1-dPP8y_V5feLr-cfLivDhcxVzepmkCWZNNx2tiNd00tiqKDM8EHztufa0JqbVjeD6aAVlgjSMZB2wYAeo7Od7zR3W9sb63PUo5qi2-p4r4J26u-Nd9dqHW4VkUxSVheDd3uDGG5mm7LaumTsOGpvw5xUIwopqCzg23_ATZijL-FUDYTRWoqmQKc7yMSQUrTDwyUE1NKlWrpUhy6L4vWfAQ78vrwCvN8Di_JgxxRlitCmFWqYxzHbu1xY_B-2IK92yCaVzh-YmrNyEV8-9M1uP-ig9Dq6pK5-lIAUQAAwIegvyyvHdA</recordid><startdate>20070821</startdate><enddate>20070821</enddate><creator>Kabayama, Kazuya</creator><creator>Sato, Takashige</creator><creator>Saito, Kumiko</creator><creator>Loberto, Nicoletta</creator><creator>Prinetti, Alessandro</creator><creator>Sonnino, Sandro</creator><creator>Kinjo, Masataka</creator><creator>Igarashi, Yasuyuki</creator><creator>Inokuchi, Jin-ichi</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070821</creationdate><title>Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance</title><author>Kabayama, Kazuya ; Sato, Takashige ; Saito, Kumiko ; Loberto, Nicoletta ; Prinetti, Alessandro ; Sonnino, Sandro ; Kinjo, Masataka ; Igarashi, Yasuyuki ; Inokuchi, Jin-ichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c589t-2426f97039c5ebeb1b6d91c3834c5fa57d5ac325c7a6fcb078e181b409e91c303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>3T3-L1 Cells</topic><topic>Adipocytes</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Biological Sciences</topic><topic>Caveolae</topic><topic>Caveolin 1 - genetics</topic><topic>Caveolin 1 - metabolism</topic><topic>Cell membranes</topic><topic>Cell Survival</topic><topic>Fluorescence</topic><topic>G(M3) Ganglioside - metabolism</topic><topic>Gangliosides</topic><topic>HEK293 cells</topic><topic>Insulin</topic><topic>Insulin Resistance</topic><topic>Lipids</topic><topic>Lysine - genetics</topic><topic>Lysine - metabolism</topic><topic>Mice</topic><topic>Protein Binding</topic><topic>Receptor, Insulin - metabolism</topic><topic>Signal Transduction</topic><topic>Spectrum analysis</topic><topic>T cell receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kabayama, Kazuya</creatorcontrib><creatorcontrib>Sato, Takashige</creatorcontrib><creatorcontrib>Saito, Kumiko</creatorcontrib><creatorcontrib>Loberto, Nicoletta</creatorcontrib><creatorcontrib>Prinetti, Alessandro</creatorcontrib><creatorcontrib>Sonnino, Sandro</creatorcontrib><creatorcontrib>Kinjo, Masataka</creatorcontrib><creatorcontrib>Igarashi, Yasuyuki</creatorcontrib><creatorcontrib>Inokuchi, Jin-ichi</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kabayama, Kazuya</au><au>Sato, Takashige</au><au>Saito, Kumiko</au><au>Loberto, Nicoletta</au><au>Prinetti, Alessandro</au><au>Sonnino, Sandro</au><au>Kinjo, Masataka</au><au>Igarashi, Yasuyuki</au><au>Inokuchi, Jin-ichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2007-08-21</date><risdate>2007</risdate><volume>104</volume><issue>34</issue><spage>13678</spage><epage>13683</epage><pages>13678-13683</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Membrane microdomains (lipid rafts) are now recognized as critical for proper compartmentalization of insulin signaling. We previously demonstrated that, in adipocytes in a state of TNFα-induced insulin resistance, the inhibition of insulin metabolic signaling and the elimination of insulin receptors (IR) from the caveolae microdomains were associated with an accumulation of the ganglioside GM3. To gain insight into molecular mechanisms behind interactions of IR, caveolin-1 (Cav1), and GM3 in adipocytes, we have performed immunoprecipitations, cross-linking studies of IR and GM3, and live cell studies using total internal reflection fluorescence microscopy and fluorescence recovery after photobleaching techniques. We found that (i) IR form complexes with Cav1 and GM3 independently; (ii) in GM3-enriched membranes the mobility of IR is increased by dissociation of the IR-Cav1 interaction; and (iii) the lysine residue localized just above the transmembrane domain of the IR β-subunit is essential for the interaction of IR with GM3. Because insulin metabolic signal transduction in adipocytes is known to be critically dependent on caveolae, we propose a pathological feature of insulin resistance in adipocytes caused by dissociation of the IR-Cav1 complex by the interactions of IR with GM3 in microdomains.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>17699617</pmid><doi>10.1073/pnas.0703650104</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2007-08, Vol.104 (34), p.13678-13683 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pnas_primary_104_34_13678_fulltext |
| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | 3T3-L1 Cells Adipocytes Animals Antibodies Biological Sciences Caveolae Caveolin 1 - genetics Caveolin 1 - metabolism Cell membranes Cell Survival Fluorescence G(M3) Ganglioside - metabolism Gangliosides HEK293 cells Insulin Insulin Resistance Lipids Lysine - genetics Lysine - metabolism Mice Protein Binding Receptor, Insulin - metabolism Signal Transduction Spectrum analysis T cell receptors |
| title | Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T21%3A13%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pnas_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Dissociation%20of%20the%20insulin%20receptor%20and%20caveolin-1%20complex%20by%20ganglioside%20GM3%20in%20the%20state%20of%20insulin%20resistance&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Kabayama,%20Kazuya&rft.date=2007-08-21&rft.volume=104&rft.issue=34&rft.spage=13678&rft.epage=13683&rft.pages=13678-13683&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.0703650104&rft_dat=%3Cjstor_pnas_%3E25436550%3C/jstor_pnas_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=201432986&rft_id=info:pmid/17699617&rft_jstor_id=25436550&rfr_iscdi=true |