Insulin stimulates movement of sorting nexin 9 between cellular compartments: a putative role mediating cell surface receptor expression and insulin action
SNX9 (sorting nexin 9) is one member of a family of proteins implicated in protein trafficking. This family is characterized by a unique PX (Phox homology) domain that includes a proline-rich sequence and an upstream phospholipid binding domain. Many sorting nexins, including SNX9, also have a C-ter...
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| Veröffentlicht in: | Biochemical journal 2003-11, Vol.376 (Pt 1), p.123-134 |
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| creator | MaCaulay, S Lance Stoichevska, Violet Grusovin, Julian Gough, Keith H Castelli, Laura A Ward, Colin W |
| description | SNX9 (sorting nexin 9) is one member of a family of proteins implicated in protein trafficking. This family is characterized by a unique PX (Phox homology) domain that includes a proline-rich sequence and an upstream phospholipid binding domain. Many sorting nexins, including SNX9, also have a C-terminal coiled region. SNX9 additionally has an N-terminal SH3 (Src homology 3) domain. Here we have investigated the cellular localization of SNX9 and the potential role it plays in insulin action. SNX9 had a cytosolic and punctate distribution, consistent with endosomal and cytosolic localization, in 3T3L1 adipocytes. It was excluded from the nucleus. The SH3 domain was responsible, at least in part, for the membrane localization of SNX9, since expression of an SH3-domain-deleted GFP (green fluorescent protein)-SNX9 fusion protein in HEK293T cells rendered the protein cytosolic. Membrane localization may also be attributed in part to the PX domain, since in vitro phospholipid binding studies demonstrated SNX9 binding to polyphosphoinositides. Insulin induced movement of SNX9 to membrane fractions from the cytosol. A GST (glutathione S-transferase)-SNX9 fusion protein was associated with IGF1 (insulin-like growth factor 1) and insulin receptors in vitro. A GFP-SNX9 fusion protein, overexpressed in 3T3L1 adipocytes, co-immunoprecipitated with insulin receptors. Furthermore, overexpression of this GFP-SNX9 fusion protein in CHOT cells decreased insulin binding, consistent with a role for SNX9 in the trafficking of insulin receptors. Microinjection of 3T3L1 cells with an antibody against SNX9 inhibited stimulation by insulin of GLUT4 translocation. These results support the involvement of SNX9 in insulin action, via an influence on the processing/trafficking of insulin receptors. A secondary role in regulation of the cellular processing, transport and/or subcellular localization of GLUT4 is also suggested. |
| doi_str_mv | 10.1042/bj20030130 |
| format | Article |
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This family is characterized by a unique PX (Phox homology) domain that includes a proline-rich sequence and an upstream phospholipid binding domain. Many sorting nexins, including SNX9, also have a C-terminal coiled region. SNX9 additionally has an N-terminal SH3 (Src homology 3) domain. Here we have investigated the cellular localization of SNX9 and the potential role it plays in insulin action. SNX9 had a cytosolic and punctate distribution, consistent with endosomal and cytosolic localization, in 3T3L1 adipocytes. It was excluded from the nucleus. The SH3 domain was responsible, at least in part, for the membrane localization of SNX9, since expression of an SH3-domain-deleted GFP (green fluorescent protein)-SNX9 fusion protein in HEK293T cells rendered the protein cytosolic. Membrane localization may also be attributed in part to the PX domain, since in vitro phospholipid binding studies demonstrated SNX9 binding to polyphosphoinositides. Insulin induced movement of SNX9 to membrane fractions from the cytosol. A GST (glutathione S-transferase)-SNX9 fusion protein was associated with IGF1 (insulin-like growth factor 1) and insulin receptors in vitro. A GFP-SNX9 fusion protein, overexpressed in 3T3L1 adipocytes, co-immunoprecipitated with insulin receptors. Furthermore, overexpression of this GFP-SNX9 fusion protein in CHOT cells decreased insulin binding, consistent with a role for SNX9 in the trafficking of insulin receptors. Microinjection of 3T3L1 cells with an antibody against SNX9 inhibited stimulation by insulin of GLUT4 translocation. These results support the involvement of SNX9 in insulin action, via an influence on the processing/trafficking of insulin receptors. A secondary role in regulation of the cellular processing, transport and/or subcellular localization of GLUT4 is also suggested.</description><identifier>ISSN: 0264-6021</identifier><identifier>EISSN: 1470-8728</identifier><identifier>DOI: 10.1042/bj20030130</identifier><identifier>PMID: 12917015</identifier><language>eng</language><publisher>England</publisher><subject>Adipocytes - chemistry ; Adipocytes - drug effects ; Adipocytes - metabolism ; Animals ; Antibodies - pharmacology ; Biological Transport ; Carrier Proteins - chemistry ; Carrier Proteins - metabolism ; Carrier Proteins - physiology ; Cell Compartmentation ; Cell Line ; Cell Membrane - metabolism ; Cytoplasmic Vesicles - chemistry ; Cytosol - metabolism ; Glucose - metabolism ; Glucose Transporter Type 4 ; Insulin - pharmacology ; Monosaccharide Transport Proteins - analysis ; Muscle Proteins ; Protein Structure, Tertiary ; Protein Transport ; Receptor, Insulin - analysis ; Receptor, Insulin - metabolism ; Receptors, Somatomedin - analysis ; Receptors, Somatomedin - metabolism ; Sorting Nexins ; Vesicular Transport Proteins</subject><ispartof>Biochemical journal, 2003-11, Vol.376 (Pt 1), p.123-134</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-96eb2f8654fd76582d140548b3e652000edbc8c9483ea6a11f4d192c525e7fb3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1223752/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1223752/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,725,778,782,883,27907,27908,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12917015$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MaCaulay, S Lance</creatorcontrib><creatorcontrib>Stoichevska, Violet</creatorcontrib><creatorcontrib>Grusovin, Julian</creatorcontrib><creatorcontrib>Gough, Keith H</creatorcontrib><creatorcontrib>Castelli, Laura A</creatorcontrib><creatorcontrib>Ward, Colin W</creatorcontrib><title>Insulin stimulates movement of sorting nexin 9 between cellular compartments: a putative role mediating cell surface receptor expression and insulin action</title><title>Biochemical journal</title><addtitle>Biochem J</addtitle><description>SNX9 (sorting nexin 9) is one member of a family of proteins implicated in protein trafficking. This family is characterized by a unique PX (Phox homology) domain that includes a proline-rich sequence and an upstream phospholipid binding domain. Many sorting nexins, including SNX9, also have a C-terminal coiled region. SNX9 additionally has an N-terminal SH3 (Src homology 3) domain. Here we have investigated the cellular localization of SNX9 and the potential role it plays in insulin action. SNX9 had a cytosolic and punctate distribution, consistent with endosomal and cytosolic localization, in 3T3L1 adipocytes. It was excluded from the nucleus. The SH3 domain was responsible, at least in part, for the membrane localization of SNX9, since expression of an SH3-domain-deleted GFP (green fluorescent protein)-SNX9 fusion protein in HEK293T cells rendered the protein cytosolic. Membrane localization may also be attributed in part to the PX domain, since in vitro phospholipid binding studies demonstrated SNX9 binding to polyphosphoinositides. Insulin induced movement of SNX9 to membrane fractions from the cytosol. A GST (glutathione S-transferase)-SNX9 fusion protein was associated with IGF1 (insulin-like growth factor 1) and insulin receptors in vitro. A GFP-SNX9 fusion protein, overexpressed in 3T3L1 adipocytes, co-immunoprecipitated with insulin receptors. Furthermore, overexpression of this GFP-SNX9 fusion protein in CHOT cells decreased insulin binding, consistent with a role for SNX9 in the trafficking of insulin receptors. Microinjection of 3T3L1 cells with an antibody against SNX9 inhibited stimulation by insulin of GLUT4 translocation. These results support the involvement of SNX9 in insulin action, via an influence on the processing/trafficking of insulin receptors. A secondary role in regulation of the cellular processing, transport and/or subcellular localization of GLUT4 is also suggested.</description><subject>Adipocytes - chemistry</subject><subject>Adipocytes - drug effects</subject><subject>Adipocytes - metabolism</subject><subject>Animals</subject><subject>Antibodies - pharmacology</subject><subject>Biological Transport</subject><subject>Carrier Proteins - chemistry</subject><subject>Carrier Proteins - metabolism</subject><subject>Carrier Proteins - physiology</subject><subject>Cell Compartmentation</subject><subject>Cell Line</subject><subject>Cell Membrane - metabolism</subject><subject>Cytoplasmic Vesicles - chemistry</subject><subject>Cytosol - metabolism</subject><subject>Glucose - metabolism</subject><subject>Glucose Transporter Type 4</subject><subject>Insulin - pharmacology</subject><subject>Monosaccharide Transport Proteins - analysis</subject><subject>Muscle Proteins</subject><subject>Protein Structure, Tertiary</subject><subject>Protein Transport</subject><subject>Receptor, Insulin - analysis</subject><subject>Receptor, Insulin - metabolism</subject><subject>Receptors, Somatomedin - analysis</subject><subject>Receptors, Somatomedin - metabolism</subject><subject>Sorting Nexins</subject><subject>Vesicular Transport Proteins</subject><issn>0264-6021</issn><issn>1470-8728</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1O3TAQha0KVG6hGx4AecWiUsr4J38skCpUWiQkNuwtx5lQo8QOtnOhz9KXrQNX0K4seT4fnzOHkGMGXxlIftY9cAABTMAHsmGyhqKpebNHNsArWVTA2QH5FOMDAJMg4SM5YLxlNbByQ_5cu7iM1tGY7LSMOmGkk9_ihC5RP9DoQ7Lunjp8zlBLO0xPiI4aHMeMB2r8NOuQVj6eU03nJelkt0iDH5FO2Fv9IrA-oHEJgzZ5hgbn5APF5zlgjNY7ql1P7c6MNilfHZH9QY8RP-_OQ3J39f3u8mdxc_vj-vLbTWGkhFS0FXZ8aKpSDn1dlQ3vc8xSNp3AqsybAew705hWNgJ1pRkbZM9abkpeYj104pBcvMrOS5f9mpwk6FHNwU46_FZeW_X_xNlf6t5vFeNc1CXPAqc7geAfF4xJTTauebVDv0RVMyEa4Cv45RU0wccYcHj7hIFaq1TvVWb45F9b7-iuO_EXNBSeig</recordid><startdate>20031115</startdate><enddate>20031115</enddate><creator>MaCaulay, S Lance</creator><creator>Stoichevska, Violet</creator><creator>Grusovin, Julian</creator><creator>Gough, Keith H</creator><creator>Castelli, Laura A</creator><creator>Ward, Colin W</creator><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>5PM</scope></search><sort><creationdate>20031115</creationdate><title>Insulin stimulates movement of sorting nexin 9 between cellular compartments: a putative role mediating cell surface receptor expression and insulin action</title><author>MaCaulay, S Lance ; Stoichevska, Violet ; Grusovin, Julian ; Gough, Keith H ; Castelli, Laura A ; Ward, Colin W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-96eb2f8654fd76582d140548b3e652000edbc8c9483ea6a11f4d192c525e7fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adipocytes - chemistry</topic><topic>Adipocytes - drug effects</topic><topic>Adipocytes - metabolism</topic><topic>Animals</topic><topic>Antibodies - pharmacology</topic><topic>Biological Transport</topic><topic>Carrier Proteins - chemistry</topic><topic>Carrier Proteins - metabolism</topic><topic>Carrier Proteins - physiology</topic><topic>Cell Compartmentation</topic><topic>Cell Line</topic><topic>Cell Membrane - metabolism</topic><topic>Cytoplasmic Vesicles - chemistry</topic><topic>Cytosol - metabolism</topic><topic>Glucose - metabolism</topic><topic>Glucose Transporter Type 4</topic><topic>Insulin - pharmacology</topic><topic>Monosaccharide Transport Proteins - analysis</topic><topic>Muscle Proteins</topic><topic>Protein Structure, Tertiary</topic><topic>Protein Transport</topic><topic>Receptor, Insulin - analysis</topic><topic>Receptor, Insulin - metabolism</topic><topic>Receptors, Somatomedin - analysis</topic><topic>Receptors, Somatomedin - metabolism</topic><topic>Sorting Nexins</topic><topic>Vesicular Transport Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MaCaulay, S Lance</creatorcontrib><creatorcontrib>Stoichevska, Violet</creatorcontrib><creatorcontrib>Grusovin, Julian</creatorcontrib><creatorcontrib>Gough, Keith H</creatorcontrib><creatorcontrib>Castelli, Laura A</creatorcontrib><creatorcontrib>Ward, Colin W</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>PubMed Central (Full Participant titles)</collection><jtitle>Biochemical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MaCaulay, S Lance</au><au>Stoichevska, Violet</au><au>Grusovin, Julian</au><au>Gough, Keith H</au><au>Castelli, Laura A</au><au>Ward, Colin W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Insulin stimulates movement of sorting nexin 9 between cellular compartments: a putative role mediating cell surface receptor expression and insulin action</atitle><jtitle>Biochemical journal</jtitle><addtitle>Biochem J</addtitle><date>2003-11-15</date><risdate>2003</risdate><volume>376</volume><issue>Pt 1</issue><spage>123</spage><epage>134</epage><pages>123-134</pages><issn>0264-6021</issn><eissn>1470-8728</eissn><abstract>SNX9 (sorting nexin 9) is one member of a family of proteins implicated in protein trafficking. This family is characterized by a unique PX (Phox homology) domain that includes a proline-rich sequence and an upstream phospholipid binding domain. Many sorting nexins, including SNX9, also have a C-terminal coiled region. SNX9 additionally has an N-terminal SH3 (Src homology 3) domain. Here we have investigated the cellular localization of SNX9 and the potential role it plays in insulin action. SNX9 had a cytosolic and punctate distribution, consistent with endosomal and cytosolic localization, in 3T3L1 adipocytes. It was excluded from the nucleus. The SH3 domain was responsible, at least in part, for the membrane localization of SNX9, since expression of an SH3-domain-deleted GFP (green fluorescent protein)-SNX9 fusion protein in HEK293T cells rendered the protein cytosolic. Membrane localization may also be attributed in part to the PX domain, since in vitro phospholipid binding studies demonstrated SNX9 binding to polyphosphoinositides. Insulin induced movement of SNX9 to membrane fractions from the cytosol. A GST (glutathione S-transferase)-SNX9 fusion protein was associated with IGF1 (insulin-like growth factor 1) and insulin receptors in vitro. A GFP-SNX9 fusion protein, overexpressed in 3T3L1 adipocytes, co-immunoprecipitated with insulin receptors. Furthermore, overexpression of this GFP-SNX9 fusion protein in CHOT cells decreased insulin binding, consistent with a role for SNX9 in the trafficking of insulin receptors. Microinjection of 3T3L1 cells with an antibody against SNX9 inhibited stimulation by insulin of GLUT4 translocation. These results support the involvement of SNX9 in insulin action, via an influence on the processing/trafficking of insulin receptors. A secondary role in regulation of the cellular processing, transport and/or subcellular localization of GLUT4 is also suggested.</abstract><cop>England</cop><pmid>12917015</pmid><doi>10.1042/bj20030130</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adipocytes - chemistry Adipocytes - drug effects Adipocytes - metabolism Animals Antibodies - pharmacology Biological Transport Carrier Proteins - chemistry Carrier Proteins - metabolism Carrier Proteins - physiology Cell Compartmentation Cell Line Cell Membrane - metabolism Cytoplasmic Vesicles - chemistry Cytosol - metabolism Glucose - metabolism Glucose Transporter Type 4 Insulin - pharmacology Monosaccharide Transport Proteins - analysis Muscle Proteins Protein Structure, Tertiary Protein Transport Receptor, Insulin - analysis Receptor, Insulin - metabolism Receptors, Somatomedin - analysis Receptors, Somatomedin - metabolism Sorting Nexins Vesicular Transport Proteins |
| title | Insulin stimulates movement of sorting nexin 9 between cellular compartments: a putative role mediating cell surface receptor expression and insulin action |
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