C5L2 Is a Functional Receptor for Acylation-stimulating Protein
C5L2 binds acylation-stimulating protein (ASP) with high affinity and is expressed in ASP-responsive cells. Functionality of C5L2 has not yet been demonstrated. Here we show that C5L2 is expressed in human subcutaneous and omental adipose tissue in both preadipocytes and adipocytes. In mice, C5L2 is...
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| Veröffentlicht in: | The Journal of biological chemistry 2005-06, Vol.280 (25), p.23936-23944 |
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| creator | Kalant, David MacLaren, Robin Cui, Wei Samanta, Ratna Monk, Peter N. Laporte, Stephane A. Cianflone, Katherine |
| description | C5L2 binds acylation-stimulating protein (ASP) with high affinity and is expressed in ASP-responsive cells. Functionality of C5L2 has not yet been demonstrated. Here we show that C5L2 is expressed in human subcutaneous and omental adipose tissue in both preadipocytes and adipocytes. In mice, C5L2 is expressed in all adipose tissues, at levels comparable with other tissues. Stable transfection of human C5L2 cDNA into HEK293 cells results in ASP stimulation of triglyceride synthesis (TGS) (193 ± 33%, 5 μm ASP, p < 0.001, where basal = 100%) and glucose transport (168 ± 21%, 10 μm ASP, p < 0.001). C3a similarly stimulates TGS (163 ± 12%, p < 0.001), but C5a and C5a des-Arg have no effect. The ASP mechanism is to increase Vmax of glucose transport (149%) and triglyceride (TG) synthesis activity (165%) through increased diacylglycerolacyltransferase activity (200%). Antisense oligonucleotide down-regulation of C5L2 in human skin fibroblasts decreases cell surface C5L2 (down to 54 ± 4% of control, p < 0.001, comparable with nonimmune background). ASP response is coordinately lost (basal TGS = 14.6 ± 1.6, with ASP = 21.0 ± 1.4 (144%), with ASP + oligonucleotides = 11.0 ± 0.8 pmol of TG/mg of cell protein, p < 0.001). In mouse 3T3-L1 preadipocytes, antisense oligonucleotides decrease C5L2 expression to 69.5 ± 0.5% of control, p < 0.001 (comparable with nonimmune) with a loss of ASP stimulation (basal TGS = 22.4 ± 2.9, with ASP = 39.6 ± 8.8 (177%), with ASP + oligonucleotides = 25.3 ± 3.0 pmol of TG/mg of cell protein, p < 0.001). C5L2 down-regulation and decreased ASP response correlate (r = 0.761, p < 0.0001 for HSF and r = 0.451, p < 0.05 for 3T3-L1). In HEK-hC5L2 expressing fluorescently tagged β-arrestin, ASP induced β-arrestin translocation to the plasma membrane and formation of endocytic complexes concurrently with increased phosphorylation of C5L2. This is the first demonstration that C5L2 is a functional receptor, mediating ASP triglyceride stimulation. |
| doi_str_mv | 10.1074/jbc.M406921200 |
| format | Article |
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Functionality of C5L2 has not yet been demonstrated. Here we show that C5L2 is expressed in human subcutaneous and omental adipose tissue in both preadipocytes and adipocytes. In mice, C5L2 is expressed in all adipose tissues, at levels comparable with other tissues. Stable transfection of human C5L2 cDNA into HEK293 cells results in ASP stimulation of triglyceride synthesis (TGS) (193 ± 33%, 5 μm ASP, p < 0.001, where basal = 100%) and glucose transport (168 ± 21%, 10 μm ASP, p < 0.001). C3a similarly stimulates TGS (163 ± 12%, p < 0.001), but C5a and C5a des-Arg have no effect. The ASP mechanism is to increase Vmax of glucose transport (149%) and triglyceride (TG) synthesis activity (165%) through increased diacylglycerolacyltransferase activity (200%). Antisense oligonucleotide down-regulation of C5L2 in human skin fibroblasts decreases cell surface C5L2 (down to 54 ± 4% of control, p < 0.001, comparable with nonimmune background). ASP response is coordinately lost (basal TGS = 14.6 ± 1.6, with ASP = 21.0 ± 1.4 (144%), with ASP + oligonucleotides = 11.0 ± 0.8 pmol of TG/mg of cell protein, p < 0.001). In mouse 3T3-L1 preadipocytes, antisense oligonucleotides decrease C5L2 expression to 69.5 ± 0.5% of control, p < 0.001 (comparable with nonimmune) with a loss of ASP stimulation (basal TGS = 22.4 ± 2.9, with ASP = 39.6 ± 8.8 (177%), with ASP + oligonucleotides = 25.3 ± 3.0 pmol of TG/mg of cell protein, p < 0.001). C5L2 down-regulation and decreased ASP response correlate (r = 0.761, p < 0.0001 for HSF and r = 0.451, p < 0.05 for 3T3-L1). In HEK-hC5L2 expressing fluorescently tagged β-arrestin, ASP induced β-arrestin translocation to the plasma membrane and formation of endocytic complexes concurrently with increased phosphorylation of C5L2. This is the first demonstration that C5L2 is a functional receptor, mediating ASP triglyceride stimulation.]]></description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M406921200</identifier><identifier>PMID: 15833747</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Arrestin - metabolism ; Base Sequence ; Cell Line ; Complement C3a - metabolism ; DNA Primers ; DNA, Complementary ; Humans ; Mice ; Protein Binding ; Receptor, Anaphylatoxin C5a ; Receptors, Chemokine - genetics ; Receptors, Chemokine - metabolism ; RNA, Messenger - genetics</subject><ispartof>The Journal of biological chemistry, 2005-06, Vol.280 (25), p.23936-23944</ispartof><rights>2005 © 2005 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-9b4e244cb6f2ccd539b4fe74a745a189be185d3e6fa316e796415fcda8fe05633</citedby><cites>FETCH-LOGICAL-c442t-9b4e244cb6f2ccd539b4fe74a745a189be185d3e6fa316e796415fcda8fe05633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15833747$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kalant, David</creatorcontrib><creatorcontrib>MacLaren, Robin</creatorcontrib><creatorcontrib>Cui, Wei</creatorcontrib><creatorcontrib>Samanta, Ratna</creatorcontrib><creatorcontrib>Monk, Peter N.</creatorcontrib><creatorcontrib>Laporte, Stephane A.</creatorcontrib><creatorcontrib>Cianflone, Katherine</creatorcontrib><title>C5L2 Is a Functional Receptor for Acylation-stimulating Protein</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description><![CDATA[C5L2 binds acylation-stimulating protein (ASP) with high affinity and is expressed in ASP-responsive cells. Functionality of C5L2 has not yet been demonstrated. Here we show that C5L2 is expressed in human subcutaneous and omental adipose tissue in both preadipocytes and adipocytes. In mice, C5L2 is expressed in all adipose tissues, at levels comparable with other tissues. Stable transfection of human C5L2 cDNA into HEK293 cells results in ASP stimulation of triglyceride synthesis (TGS) (193 ± 33%, 5 μm ASP, p < 0.001, where basal = 100%) and glucose transport (168 ± 21%, 10 μm ASP, p < 0.001). C3a similarly stimulates TGS (163 ± 12%, p < 0.001), but C5a and C5a des-Arg have no effect. The ASP mechanism is to increase Vmax of glucose transport (149%) and triglyceride (TG) synthesis activity (165%) through increased diacylglycerolacyltransferase activity (200%). Antisense oligonucleotide down-regulation of C5L2 in human skin fibroblasts decreases cell surface C5L2 (down to 54 ± 4% of control, p < 0.001, comparable with nonimmune background). ASP response is coordinately lost (basal TGS = 14.6 ± 1.6, with ASP = 21.0 ± 1.4 (144%), with ASP + oligonucleotides = 11.0 ± 0.8 pmol of TG/mg of cell protein, p < 0.001). In mouse 3T3-L1 preadipocytes, antisense oligonucleotides decrease C5L2 expression to 69.5 ± 0.5% of control, p < 0.001 (comparable with nonimmune) with a loss of ASP stimulation (basal TGS = 22.4 ± 2.9, with ASP = 39.6 ± 8.8 (177%), with ASP + oligonucleotides = 25.3 ± 3.0 pmol of TG/mg of cell protein, p < 0.001). C5L2 down-regulation and decreased ASP response correlate (r = 0.761, p < 0.0001 for HSF and r = 0.451, p < 0.05 for 3T3-L1). In HEK-hC5L2 expressing fluorescently tagged β-arrestin, ASP induced β-arrestin translocation to the plasma membrane and formation of endocytic complexes concurrently with increased phosphorylation of C5L2. This is the first demonstration that C5L2 is a functional receptor, mediating ASP triglyceride stimulation.]]></description><subject>Animals</subject><subject>Arrestin - metabolism</subject><subject>Base Sequence</subject><subject>Cell Line</subject><subject>Complement C3a - metabolism</subject><subject>DNA Primers</subject><subject>DNA, Complementary</subject><subject>Humans</subject><subject>Mice</subject><subject>Protein Binding</subject><subject>Receptor, Anaphylatoxin C5a</subject><subject>Receptors, Chemokine - genetics</subject><subject>Receptors, Chemokine - metabolism</subject><subject>RNA, Messenger - genetics</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtLAzEQh4MoWqtXj7IH8bY17-yeRIqPQkURBW8hm521Kfuoya7if29KCz2JA2GG5PsN4UPojOAJwYpfLQs7eeRY5pRQjPfQiOCMpUyQ9300wpiSNKciO0LHISxxLJ6TQ3RERMaY4mqErqdiTpNZSExyN7S2d11r6uQFLKz6zidVPDf2pzbrhzT0rhnWc_uRPPuuB9eeoIPK1AFOt32M3u5uX6cP6fzpfja9maeWc9qnecGBcm4LWVFrS8HiRQWKG8WFIVleAMlEyUBWhhEJKpeciMqWJqsAC8nYGF1u9q589zlA6HXjgoW6Ni10Q9BS5VwyTv4FiRLRgVIRnGxA67sQPFR65V1j_I8mWK_d6uhW79zGwPl281A0UO7wrcwIXGyAhftYfDsPunCdXUCjaYY1FZqynMmIZRsMoq8vB14H66C1UMaI7XXZub--8AtFCJJF</recordid><startdate>20050624</startdate><enddate>20050624</enddate><creator>Kalant, David</creator><creator>MacLaren, Robin</creator><creator>Cui, Wei</creator><creator>Samanta, Ratna</creator><creator>Monk, Peter N.</creator><creator>Laporte, Stephane A.</creator><creator>Cianflone, Katherine</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20050624</creationdate><title>C5L2 Is a Functional Receptor for Acylation-stimulating Protein</title><author>Kalant, David ; MacLaren, Robin ; Cui, Wei ; Samanta, Ratna ; Monk, Peter N. ; Laporte, Stephane A. ; Cianflone, Katherine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-9b4e244cb6f2ccd539b4fe74a745a189be185d3e6fa316e796415fcda8fe05633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Arrestin - metabolism</topic><topic>Base Sequence</topic><topic>Cell Line</topic><topic>Complement C3a - metabolism</topic><topic>DNA Primers</topic><topic>DNA, Complementary</topic><topic>Humans</topic><topic>Mice</topic><topic>Protein Binding</topic><topic>Receptor, Anaphylatoxin C5a</topic><topic>Receptors, Chemokine - genetics</topic><topic>Receptors, Chemokine - metabolism</topic><topic>RNA, Messenger - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kalant, David</creatorcontrib><creatorcontrib>MacLaren, Robin</creatorcontrib><creatorcontrib>Cui, Wei</creatorcontrib><creatorcontrib>Samanta, Ratna</creatorcontrib><creatorcontrib>Monk, Peter N.</creatorcontrib><creatorcontrib>Laporte, Stephane A.</creatorcontrib><creatorcontrib>Cianflone, Katherine</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kalant, David</au><au>MacLaren, Robin</au><au>Cui, Wei</au><au>Samanta, Ratna</au><au>Monk, Peter N.</au><au>Laporte, Stephane A.</au><au>Cianflone, Katherine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>C5L2 Is a Functional Receptor for Acylation-stimulating Protein</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2005-06-24</date><risdate>2005</risdate><volume>280</volume><issue>25</issue><spage>23936</spage><epage>23944</epage><pages>23936-23944</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract><![CDATA[C5L2 binds acylation-stimulating protein (ASP) with high affinity and is expressed in ASP-responsive cells. Functionality of C5L2 has not yet been demonstrated. Here we show that C5L2 is expressed in human subcutaneous and omental adipose tissue in both preadipocytes and adipocytes. In mice, C5L2 is expressed in all adipose tissues, at levels comparable with other tissues. Stable transfection of human C5L2 cDNA into HEK293 cells results in ASP stimulation of triglyceride synthesis (TGS) (193 ± 33%, 5 μm ASP, p < 0.001, where basal = 100%) and glucose transport (168 ± 21%, 10 μm ASP, p < 0.001). C3a similarly stimulates TGS (163 ± 12%, p < 0.001), but C5a and C5a des-Arg have no effect. The ASP mechanism is to increase Vmax of glucose transport (149%) and triglyceride (TG) synthesis activity (165%) through increased diacylglycerolacyltransferase activity (200%). Antisense oligonucleotide down-regulation of C5L2 in human skin fibroblasts decreases cell surface C5L2 (down to 54 ± 4% of control, p < 0.001, comparable with nonimmune background). ASP response is coordinately lost (basal TGS = 14.6 ± 1.6, with ASP = 21.0 ± 1.4 (144%), with ASP + oligonucleotides = 11.0 ± 0.8 pmol of TG/mg of cell protein, p < 0.001). In mouse 3T3-L1 preadipocytes, antisense oligonucleotides decrease C5L2 expression to 69.5 ± 0.5% of control, p < 0.001 (comparable with nonimmune) with a loss of ASP stimulation (basal TGS = 22.4 ± 2.9, with ASP = 39.6 ± 8.8 (177%), with ASP + oligonucleotides = 25.3 ± 3.0 pmol of TG/mg of cell protein, p < 0.001). C5L2 down-regulation and decreased ASP response correlate (r = 0.761, p < 0.0001 for HSF and r = 0.451, p < 0.05 for 3T3-L1). In HEK-hC5L2 expressing fluorescently tagged β-arrestin, ASP induced β-arrestin translocation to the plasma membrane and formation of endocytic complexes concurrently with increased phosphorylation of C5L2. This is the first demonstration that C5L2 is a functional receptor, mediating ASP triglyceride stimulation.]]></abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15833747</pmid><doi>10.1074/jbc.M406921200</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Arrestin - metabolism Base Sequence Cell Line Complement C3a - metabolism DNA Primers DNA, Complementary Humans Mice Protein Binding Receptor, Anaphylatoxin C5a Receptors, Chemokine - genetics Receptors, Chemokine - metabolism RNA, Messenger - genetics |
| title | C5L2 Is a Functional Receptor for Acylation-stimulating Protein |
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