Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell surface and lipid bodies
Caveolins are a crucial component of plasma membrane (PM) caveolae but have also been localized to intracellular compartments, including the Golgi complex and lipid bodies. Mutant caveolins associated with human disease show aberrant trafficking to the PM and Golgi accumulation. We now show that the...
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Veröffentlicht in: | Molecular biology of the cell 2005-04, Vol.16 (4), p.2091-2105 |
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creator | Pol, Albert Martin, Sally Fernández, Manuel A Ingelmo-Torres, Mercedes Ferguson, Charles Enrich, Carlos Parton, Robert G |
description | Caveolins are a crucial component of plasma membrane (PM) caveolae but have also been localized to intracellular compartments, including the Golgi complex and lipid bodies. Mutant caveolins associated with human disease show aberrant trafficking to the PM and Golgi accumulation. We now show that the Golgi pool of mainly newly synthesized protein is detergent-soluble and predominantly in a monomeric state, in contrast to the surface pool. Caveolin at the PM is not recognized by specific caveolin antibodies unless PM cholesterol is depleted. Exit from the Golgi complex of wild-type caveolin-1 or -3, but not vesicular stomatitis virus-G protein, is modulated by changing cellular cholesterol levels. In contrast, a muscular dystrophy-associated mutant of caveolin-3, Cav3P104L, showed increased accumulation in the Golgi complex upon cholesterol treatment. In addition, we demonstrate that in response to fatty acid treatment caveolin can follow a previously undescribed pathway from the PM to lipid bodies and can move from lipid bodies to the PM in response to removal of fatty acids. The results suggest that cholesterol is a rate-limiting component for caveolin trafficking. Changes in caveolin flux through the exocytic pathway can therefore be an indicator of cellular cholesterol and fatty acid levels. |
doi_str_mv | 10.1091/mbc.e04-08-0737 |
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Mutant caveolins associated with human disease show aberrant trafficking to the PM and Golgi accumulation. We now show that the Golgi pool of mainly newly synthesized protein is detergent-soluble and predominantly in a monomeric state, in contrast to the surface pool. Caveolin at the PM is not recognized by specific caveolin antibodies unless PM cholesterol is depleted. Exit from the Golgi complex of wild-type caveolin-1 or -3, but not vesicular stomatitis virus-G protein, is modulated by changing cellular cholesterol levels. In contrast, a muscular dystrophy-associated mutant of caveolin-3, Cav3P104L, showed increased accumulation in the Golgi complex upon cholesterol treatment. In addition, we demonstrate that in response to fatty acid treatment caveolin can follow a previously undescribed pathway from the PM to lipid bodies and can move from lipid bodies to the PM in response to removal of fatty acids. The results suggest that cholesterol is a rate-limiting component for caveolin trafficking. Changes in caveolin flux through the exocytic pathway can therefore be an indicator of cellular cholesterol and fatty acid levels.</description><identifier>ISSN: 1059-1524</identifier><identifier>EISSN: 1939-4586</identifier><identifier>DOI: 10.1091/mbc.e04-08-0737</identifier><identifier>PMID: 15689493</identifier><language>eng</language><publisher>United States: American Society for Cell Biology</publisher><subject>Animals ; Aparell de Golgi ; Caveolin 1 ; Caveolin 3 ; Caveolins - genetics ; Caveolins - metabolism ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Cells, Cultured ; Cercopithecus aethiops ; Cholesterol ; Cholesterol - metabolism ; Colesterol ; Cricetinae ; Fatty acids ; Fatty Acids - metabolism ; Golgi apparatus ; Golgi Apparatus - drug effects ; Golgi Apparatus - metabolism ; Membrane proteins ; Methanol - chemistry ; Methanol - pharmacology ; Microscopy, Video ; Molecular Weight ; Octoxynol - chemistry ; Octoxynol - pharmacology ; Protein Transport ; Proteïnes de membrana ; Solubility - drug effects ; Temperature ; Time Factors ; Àcids grassos</subject><ispartof>Molecular biology of the cell, 2005-04, Vol.16 (4), p.2091-2105</ispartof><rights>cc-by-nc-sa, (c) Pol et al., 2005 info:eu-repo/semantics/openAccess <a href="http://creativecommons.org/licenses/cc-by-nc-sa/3.0/es">http://creativecommons.org/licenses/cc-by-nc-sa/3.0/es</a></rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c521t-267a6175bd2206318d16e45bff87cf130a7d5259d89cbf69780664608b9b74203</citedby><cites>FETCH-LOGICAL-c521t-267a6175bd2206318d16e45bff87cf130a7d5259d89cbf69780664608b9b74203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,26974,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15689493$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pol, Albert</creatorcontrib><creatorcontrib>Martin, Sally</creatorcontrib><creatorcontrib>Fernández, Manuel A</creatorcontrib><creatorcontrib>Ingelmo-Torres, Mercedes</creatorcontrib><creatorcontrib>Ferguson, Charles</creatorcontrib><creatorcontrib>Enrich, Carlos</creatorcontrib><creatorcontrib>Parton, Robert G</creatorcontrib><title>Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell surface and lipid bodies</title><title>Molecular biology of the cell</title><addtitle>Mol Biol Cell</addtitle><description>Caveolins are a crucial component of plasma membrane (PM) caveolae but have also been localized to intracellular compartments, including the Golgi complex and lipid bodies. Mutant caveolins associated with human disease show aberrant trafficking to the PM and Golgi accumulation. We now show that the Golgi pool of mainly newly synthesized protein is detergent-soluble and predominantly in a monomeric state, in contrast to the surface pool. Caveolin at the PM is not recognized by specific caveolin antibodies unless PM cholesterol is depleted. Exit from the Golgi complex of wild-type caveolin-1 or -3, but not vesicular stomatitis virus-G protein, is modulated by changing cellular cholesterol levels. In contrast, a muscular dystrophy-associated mutant of caveolin-3, Cav3P104L, showed increased accumulation in the Golgi complex upon cholesterol treatment. In addition, we demonstrate that in response to fatty acid treatment caveolin can follow a previously undescribed pathway from the PM to lipid bodies and can move from lipid bodies to the PM in response to removal of fatty acids. The results suggest that cholesterol is a rate-limiting component for caveolin trafficking. Changes in caveolin flux through the exocytic pathway can therefore be an indicator of cellular cholesterol and fatty acid levels.</description><subject>Animals</subject><subject>Aparell de Golgi</subject><subject>Caveolin 1</subject><subject>Caveolin 3</subject><subject>Caveolins - genetics</subject><subject>Caveolins - metabolism</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - metabolism</subject><subject>Cells, Cultured</subject><subject>Cercopithecus aethiops</subject><subject>Cholesterol</subject><subject>Cholesterol - metabolism</subject><subject>Colesterol</subject><subject>Cricetinae</subject><subject>Fatty acids</subject><subject>Fatty Acids - metabolism</subject><subject>Golgi apparatus</subject><subject>Golgi Apparatus - drug effects</subject><subject>Golgi Apparatus - metabolism</subject><subject>Membrane proteins</subject><subject>Methanol - chemistry</subject><subject>Methanol - pharmacology</subject><subject>Microscopy, Video</subject><subject>Molecular Weight</subject><subject>Octoxynol - chemistry</subject><subject>Octoxynol - pharmacology</subject><subject>Protein Transport</subject><subject>Proteïnes de membrana</subject><subject>Solubility - drug effects</subject><subject>Temperature</subject><subject>Time Factors</subject><subject>Àcids grassos</subject><issn>1059-1524</issn><issn>1939-4586</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>XX2</sourceid><recordid>eNpFkc9vFCEUx0ljY2vr2Zvh5G1aYPgxHM1Gq0kTL3omDDx2qcywwoy6f4L_tex2kx7Ig7zv90ve-yD0jpI7SjS9n0Z3B4R3ZOiI6tUFuqa61x0Xg3zV7kTojgrGr9CbWp8IoZxL9RpdUSEHzXV_jf5tdjlBXaDkhO3scbDLcsDWRV9xge2a7ALYH2Y7RYed_Q05xRkvxYYQ3c84b_GyK3nd7loF_JDTNmKXp32Cv6e8EZY_APOp6yAlXNcSrINTM8V9bJLsI9RbdBlsqvD2XG_Qj8-fvm--dI_fHr5uPj52TjC6dEwqK6kSo2eMyJ4OnkrgYgxhUC7QnljlBRPaD9qNQWo1ECm5JMOoR8UZ6W8Qfc51dXWmgIPi7GKyjS-P42FEMUO17KVsng_Pnn3Jv9a2LjPFepzGzpDXaqQSUrdvmvD-HF5yrQWC2Zc42XIwlJgjMdOImUbMkMEciTXH-3P0Ok7gX_RnRP1_g2OTmA</recordid><startdate>20050401</startdate><enddate>20050401</enddate><creator>Pol, Albert</creator><creator>Martin, Sally</creator><creator>Fernández, Manuel A</creator><creator>Ingelmo-Torres, Mercedes</creator><creator>Ferguson, Charles</creator><creator>Enrich, Carlos</creator><creator>Parton, Robert G</creator><general>American Society for Cell Biology</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><scope>XX2</scope></search><sort><creationdate>20050401</creationdate><title>Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell surface and lipid bodies</title><author>Pol, Albert ; Martin, Sally ; Fernández, Manuel A ; Ingelmo-Torres, Mercedes ; Ferguson, Charles ; Enrich, Carlos ; Parton, Robert G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c521t-267a6175bd2206318d16e45bff87cf130a7d5259d89cbf69780664608b9b74203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Aparell de Golgi</topic><topic>Caveolin 1</topic><topic>Caveolin 3</topic><topic>Caveolins - genetics</topic><topic>Caveolins - metabolism</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>Cells, Cultured</topic><topic>Cercopithecus aethiops</topic><topic>Cholesterol</topic><topic>Cholesterol - metabolism</topic><topic>Colesterol</topic><topic>Cricetinae</topic><topic>Fatty acids</topic><topic>Fatty Acids - metabolism</topic><topic>Golgi apparatus</topic><topic>Golgi Apparatus - drug effects</topic><topic>Golgi Apparatus - metabolism</topic><topic>Membrane proteins</topic><topic>Methanol - chemistry</topic><topic>Methanol - pharmacology</topic><topic>Microscopy, Video</topic><topic>Molecular Weight</topic><topic>Octoxynol - chemistry</topic><topic>Octoxynol - pharmacology</topic><topic>Protein Transport</topic><topic>Proteïnes de membrana</topic><topic>Solubility - drug effects</topic><topic>Temperature</topic><topic>Time Factors</topic><topic>Àcids grassos</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pol, Albert</creatorcontrib><creatorcontrib>Martin, Sally</creatorcontrib><creatorcontrib>Fernández, Manuel A</creatorcontrib><creatorcontrib>Ingelmo-Torres, Mercedes</creatorcontrib><creatorcontrib>Ferguson, Charles</creatorcontrib><creatorcontrib>Enrich, Carlos</creatorcontrib><creatorcontrib>Parton, Robert G</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><collection>Recercat</collection><jtitle>Molecular biology of the cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pol, Albert</au><au>Martin, Sally</au><au>Fernández, Manuel A</au><au>Ingelmo-Torres, Mercedes</au><au>Ferguson, Charles</au><au>Enrich, Carlos</au><au>Parton, Robert G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell surface and lipid bodies</atitle><jtitle>Molecular biology of the cell</jtitle><addtitle>Mol Biol Cell</addtitle><date>2005-04-01</date><risdate>2005</risdate><volume>16</volume><issue>4</issue><spage>2091</spage><epage>2105</epage><pages>2091-2105</pages><issn>1059-1524</issn><eissn>1939-4586</eissn><abstract>Caveolins are a crucial component of plasma membrane (PM) caveolae but have also been localized to intracellular compartments, including the Golgi complex and lipid bodies. Mutant caveolins associated with human disease show aberrant trafficking to the PM and Golgi accumulation. We now show that the Golgi pool of mainly newly synthesized protein is detergent-soluble and predominantly in a monomeric state, in contrast to the surface pool. Caveolin at the PM is not recognized by specific caveolin antibodies unless PM cholesterol is depleted. Exit from the Golgi complex of wild-type caveolin-1 or -3, but not vesicular stomatitis virus-G protein, is modulated by changing cellular cholesterol levels. In contrast, a muscular dystrophy-associated mutant of caveolin-3, Cav3P104L, showed increased accumulation in the Golgi complex upon cholesterol treatment. In addition, we demonstrate that in response to fatty acid treatment caveolin can follow a previously undescribed pathway from the PM to lipid bodies and can move from lipid bodies to the PM in response to removal of fatty acids. The results suggest that cholesterol is a rate-limiting component for caveolin trafficking. Changes in caveolin flux through the exocytic pathway can therefore be an indicator of cellular cholesterol and fatty acid levels.</abstract><cop>United States</cop><pub>American Society for Cell Biology</pub><pmid>15689493</pmid><doi>10.1091/mbc.e04-08-0737</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Aparell de Golgi Caveolin 1 Caveolin 3 Caveolins - genetics Caveolins - metabolism Cell Membrane - drug effects Cell Membrane - metabolism Cells, Cultured Cercopithecus aethiops Cholesterol Cholesterol - metabolism Colesterol Cricetinae Fatty acids Fatty Acids - metabolism Golgi apparatus Golgi Apparatus - drug effects Golgi Apparatus - metabolism Membrane proteins Methanol - chemistry Methanol - pharmacology Microscopy, Video Molecular Weight Octoxynol - chemistry Octoxynol - pharmacology Protein Transport Proteïnes de membrana Solubility - drug effects Temperature Time Factors Àcids grassos |
title | Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell surface and lipid bodies |
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