Caveolar Internalization of Growth Hormone
Caveolae are plasma membrane specializations formed by caveolin and characterized by their dependence on membrane cholesterol for structural integrity. We have investigated the role of caveolae in the internalization of GH in CHO cells stably transfected with GH receptor cDNA (CHO–GHR1–638). We show...
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| Veröffentlicht in: | Experimental cell research 1999-01, Vol.246 (1), p.47-55 |
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| creator | Lobie, Peter E. Sadir, Rabia Graichen, Ralph Mertani, Hichem C. Morel, Gérard |
| description | Caveolae are plasma membrane specializations formed by caveolin and characterized by their dependence on membrane cholesterol for structural integrity. We have investigated the role of caveolae in the internalization of GH in CHO cells stably transfected with GH receptor cDNA (CHO–GHR1–638). We show by immunogold electron microscopy that a portion of the GH receptor at the cell surface is localized to or near caveolin-containing structures and upon GH stimulation the receptor aggregates in caveolae. Similarly the hormone is observed to be aggregated in caveolae and a portion of the hormone is internalized into the cell in caveolin-containing vesicles. Disruption of caveolar integrity by sterol-binding agents (filipin, nystatin) partially inhibits internalization of125I-hGH whereas internalization of hormone is not affected by non-sterol-binding agents which also insert into the cell membrane (polymyxin B, xylazine). Transient transfection of caveolin cDNA into CHO cells concomitantly transfected with GH receptor cDNA increases both the internalization of hormone and the GH stimulation of STAT-mediated transcription. In conclusion, we demonstrate that caveolae constitute one pathway for the internalization of GH. Such an internalization pathway may also be utilized by other members of the cytokine receptor superfamily. |
| doi_str_mv | 10.1006/excr.1998.4288 |
| format | Article |
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We have investigated the role of caveolae in the internalization of GH in CHO cells stably transfected with GH receptor cDNA (CHO–GHR1–638). We show by immunogold electron microscopy that a portion of the GH receptor at the cell surface is localized to or near caveolin-containing structures and upon GH stimulation the receptor aggregates in caveolae. Similarly the hormone is observed to be aggregated in caveolae and a portion of the hormone is internalized into the cell in caveolin-containing vesicles. Disruption of caveolar integrity by sterol-binding agents (filipin, nystatin) partially inhibits internalization of125I-hGH whereas internalization of hormone is not affected by non-sterol-binding agents which also insert into the cell membrane (polymyxin B, xylazine). Transient transfection of caveolin cDNA into CHO cells concomitantly transfected with GH receptor cDNA increases both the internalization of hormone and the GH stimulation of STAT-mediated transcription. In conclusion, we demonstrate that caveolae constitute one pathway for the internalization of GH. Such an internalization pathway may also be utilized by other members of the cytokine receptor superfamily.</description><identifier>ISSN: 0014-4827</identifier><identifier>EISSN: 1090-2422</identifier><identifier>DOI: 10.1006/excr.1998.4288</identifier><identifier>PMID: 9882514</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Caveolin 1 ; Caveolins ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Cell Membrane - ultrastructure ; CHO Cells ; Cholesterol - metabolism ; Cricetinae ; DNA-Binding Proteins - metabolism ; Endocytosis - drug effects ; Endocytosis - physiology ; Filipin - pharmacology ; Gene Expression Regulation - drug effects ; Growth Hormone - metabolism ; Growth Hormone - pharmacology ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Membrane Proteins - ultrastructure ; Microscopy, Electron ; Nystatin - pharmacology ; Polymyxin B - pharmacology ; Receptor Aggregation - drug effects ; Receptors, Somatotropin - genetics ; Receptors, Somatotropin - metabolism ; Receptors, Somatotropin - ultrastructure ; Signal Transduction - drug effects ; Solubility ; STAT1 Transcription Factor ; Trans-Activators - metabolism ; Transfection ; Xylazine - pharmacology</subject><ispartof>Experimental cell research, 1999-01, Vol.246 (1), p.47-55</ispartof><rights>1999 Academic Press</rights><rights>Copyright 1999 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c339t-e12255d89101ce8696769de6fd071915f5d212bf48839a6d042223b2a131f7093</citedby><cites>FETCH-LOGICAL-c339t-e12255d89101ce8696769de6fd071915f5d212bf48839a6d042223b2a131f7093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/excr.1998.4288$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9882514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lobie, Peter E.</creatorcontrib><creatorcontrib>Sadir, Rabia</creatorcontrib><creatorcontrib>Graichen, Ralph</creatorcontrib><creatorcontrib>Mertani, Hichem C.</creatorcontrib><creatorcontrib>Morel, Gérard</creatorcontrib><title>Caveolar Internalization of Growth Hormone</title><title>Experimental cell research</title><addtitle>Exp Cell Res</addtitle><description>Caveolae are plasma membrane specializations formed by caveolin and characterized by their dependence on membrane cholesterol for structural integrity. We have investigated the role of caveolae in the internalization of GH in CHO cells stably transfected with GH receptor cDNA (CHO–GHR1–638). We show by immunogold electron microscopy that a portion of the GH receptor at the cell surface is localized to or near caveolin-containing structures and upon GH stimulation the receptor aggregates in caveolae. Similarly the hormone is observed to be aggregated in caveolae and a portion of the hormone is internalized into the cell in caveolin-containing vesicles. Disruption of caveolar integrity by sterol-binding agents (filipin, nystatin) partially inhibits internalization of125I-hGH whereas internalization of hormone is not affected by non-sterol-binding agents which also insert into the cell membrane (polymyxin B, xylazine). Transient transfection of caveolin cDNA into CHO cells concomitantly transfected with GH receptor cDNA increases both the internalization of hormone and the GH stimulation of STAT-mediated transcription. In conclusion, we demonstrate that caveolae constitute one pathway for the internalization of GH. Such an internalization pathway may also be utilized by other members of the cytokine receptor superfamily.</description><subject>Animals</subject><subject>Caveolin 1</subject><subject>Caveolins</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - metabolism</subject><subject>Cell Membrane - ultrastructure</subject><subject>CHO Cells</subject><subject>Cholesterol - metabolism</subject><subject>Cricetinae</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Endocytosis - drug effects</subject><subject>Endocytosis - physiology</subject><subject>Filipin - pharmacology</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Growth Hormone - metabolism</subject><subject>Growth Hormone - pharmacology</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Membrane Proteins - ultrastructure</subject><subject>Microscopy, Electron</subject><subject>Nystatin - pharmacology</subject><subject>Polymyxin B - pharmacology</subject><subject>Receptor Aggregation - drug effects</subject><subject>Receptors, Somatotropin - genetics</subject><subject>Receptors, Somatotropin - metabolism</subject><subject>Receptors, Somatotropin - ultrastructure</subject><subject>Signal Transduction - drug effects</subject><subject>Solubility</subject><subject>STAT1 Transcription Factor</subject><subject>Trans-Activators - metabolism</subject><subject>Transfection</subject><subject>Xylazine - pharmacology</subject><issn>0014-4827</issn><issn>1090-2422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kD1PwzAQhi0EKqWwsiFlYkBK8Efs2COqoK1UiQVmy7UvwiiJi52Wj19PolZsTDe8z726exC6JrggGIt7-LKxIErJoqRSnqApwQrntKT0FE0xJmVeSlqdo4uU3jHGUhIxQRMlJeWknKK7udlDaEzMVl0PsTON_zG9D10W6mwRw2f_li1DbEMHl-isNk2Cq-Ocodenx5f5Ml8_L1bzh3VuGVN9DoRSzp1UBBMLUihRCeVA1A5XRBFec0cJ3dSllEwZ4fBwKmUbaggjdYUVm6HbQ-82ho8dpF63PlloGtNB2CUtFOdMcjaAxQG0MaQUodbb6FsTvzXBepSjRzl6lKNHOcPCzbF5t2nB_eFHG0MuDzkM7-09RJ2sh86C8xFsr13w_1X_AgyOcUg</recordid><startdate>19990110</startdate><enddate>19990110</enddate><creator>Lobie, Peter E.</creator><creator>Sadir, Rabia</creator><creator>Graichen, Ralph</creator><creator>Mertani, Hichem C.</creator><creator>Morel, Gérard</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>19990110</creationdate><title>Caveolar Internalization of Growth Hormone</title><author>Lobie, Peter E. ; Sadir, Rabia ; Graichen, Ralph ; Mertani, Hichem C. ; Morel, Gérard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c339t-e12255d89101ce8696769de6fd071915f5d212bf48839a6d042223b2a131f7093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Caveolin 1</topic><topic>Caveolins</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>Cell Membrane - ultrastructure</topic><topic>CHO Cells</topic><topic>Cholesterol - metabolism</topic><topic>Cricetinae</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Endocytosis - drug effects</topic><topic>Endocytosis - physiology</topic><topic>Filipin - pharmacology</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Growth Hormone - metabolism</topic><topic>Growth Hormone - pharmacology</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Membrane Proteins - ultrastructure</topic><topic>Microscopy, Electron</topic><topic>Nystatin - pharmacology</topic><topic>Polymyxin B - pharmacology</topic><topic>Receptor Aggregation - drug effects</topic><topic>Receptors, Somatotropin - genetics</topic><topic>Receptors, Somatotropin - metabolism</topic><topic>Receptors, Somatotropin - ultrastructure</topic><topic>Signal Transduction - drug effects</topic><topic>Solubility</topic><topic>STAT1 Transcription Factor</topic><topic>Trans-Activators - metabolism</topic><topic>Transfection</topic><topic>Xylazine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lobie, Peter E.</creatorcontrib><creatorcontrib>Sadir, Rabia</creatorcontrib><creatorcontrib>Graichen, Ralph</creatorcontrib><creatorcontrib>Mertani, Hichem C.</creatorcontrib><creatorcontrib>Morel, Gérard</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental cell research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lobie, Peter E.</au><au>Sadir, Rabia</au><au>Graichen, Ralph</au><au>Mertani, Hichem C.</au><au>Morel, Gérard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Caveolar Internalization of Growth Hormone</atitle><jtitle>Experimental cell research</jtitle><addtitle>Exp Cell Res</addtitle><date>1999-01-10</date><risdate>1999</risdate><volume>246</volume><issue>1</issue><spage>47</spage><epage>55</epage><pages>47-55</pages><issn>0014-4827</issn><eissn>1090-2422</eissn><abstract>Caveolae are plasma membrane specializations formed by caveolin and characterized by their dependence on membrane cholesterol for structural integrity. We have investigated the role of caveolae in the internalization of GH in CHO cells stably transfected with GH receptor cDNA (CHO–GHR1–638). We show by immunogold electron microscopy that a portion of the GH receptor at the cell surface is localized to or near caveolin-containing structures and upon GH stimulation the receptor aggregates in caveolae. Similarly the hormone is observed to be aggregated in caveolae and a portion of the hormone is internalized into the cell in caveolin-containing vesicles. Disruption of caveolar integrity by sterol-binding agents (filipin, nystatin) partially inhibits internalization of125I-hGH whereas internalization of hormone is not affected by non-sterol-binding agents which also insert into the cell membrane (polymyxin B, xylazine). Transient transfection of caveolin cDNA into CHO cells concomitantly transfected with GH receptor cDNA increases both the internalization of hormone and the GH stimulation of STAT-mediated transcription. In conclusion, we demonstrate that caveolae constitute one pathway for the internalization of GH. Such an internalization pathway may also be utilized by other members of the cytokine receptor superfamily.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>9882514</pmid><doi>10.1006/excr.1998.4288</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Caveolin 1 Caveolins Cell Membrane - drug effects Cell Membrane - metabolism Cell Membrane - ultrastructure CHO Cells Cholesterol - metabolism Cricetinae DNA-Binding Proteins - metabolism Endocytosis - drug effects Endocytosis - physiology Filipin - pharmacology Gene Expression Regulation - drug effects Growth Hormone - metabolism Growth Hormone - pharmacology Membrane Proteins - genetics Membrane Proteins - metabolism Membrane Proteins - ultrastructure Microscopy, Electron Nystatin - pharmacology Polymyxin B - pharmacology Receptor Aggregation - drug effects Receptors, Somatotropin - genetics Receptors, Somatotropin - metabolism Receptors, Somatotropin - ultrastructure Signal Transduction - drug effects Solubility STAT1 Transcription Factor Trans-Activators - metabolism Transfection Xylazine - pharmacology |
| title | Caveolar Internalization of Growth Hormone |
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