Deletion mutant of FGFR4 induces onion-like membrane structures in the nucleus
The expression of several deletion mutants of fibroblast growth factor receptor 4 (FGFR4) was studied in COS-1 cells. FGFR4-mutants lacking most of the extracellular region did not efficiently reach the plasma membrane but accumulated in the endoplasmic reticulum (ER) and Golgi body. A mutant FGFR4...
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Veröffentlicht in: | Journal of cell science 2004-04, Vol.117 (Pt 9), p.1807-1819 |
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creator | Sørensen, Vigdis Brech, Andreas Khnykin, Denis Kolpakova, Elona Citores, Lucia Olsnes, Sjur |
description | The expression of several deletion mutants of fibroblast growth factor receptor 4 (FGFR4) was studied in COS-1 cells. FGFR4-mutants lacking most of the extracellular region did not efficiently reach the plasma membrane but accumulated in the endoplasmic reticulum (ER) and Golgi body. A mutant FGFR4 lacking the kinase domain as well as most of the extracellular region (DeltaExt/R4Tth) had a distinct intracellular distribution. It localized in part to the nucleus, where it exhibited a striking spotted pattern. Ultrastructural studies showed that the nuclear spots consisted of several layers of membrane that were folded into onion-like structures at the nucleoplasmic side of the nuclear envelope. These intranuclear structures did not contain nuclear pores but were positive for the ER proteins calreticulin and protein disulfide isomerase, in addition to abundant DeltaExt/R4Tth. Formation of the intranuclear structures was sensitive to inhibition of protein kinase C. Live microscopy of a green-fluorescent-protein/DeltaExt/R4Tth fusion protein showed that the intranuclear structures were stable and immobile, suggesting that they function as deposits of the overexpressed mutant and associated membrane. The DeltaExt/R4Tth protein also induced formation of densely packed membrane stacks in the cytosol and we suggest a model were the intranuclear structures are formed by invagination of ER-derived membrane stacks into the nucleus. |
doi_str_mv | 10.1242/jcs.01047 |
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FGFR4-mutants lacking most of the extracellular region did not efficiently reach the plasma membrane but accumulated in the endoplasmic reticulum (ER) and Golgi body. A mutant FGFR4 lacking the kinase domain as well as most of the extracellular region (DeltaExt/R4Tth) had a distinct intracellular distribution. It localized in part to the nucleus, where it exhibited a striking spotted pattern. Ultrastructural studies showed that the nuclear spots consisted of several layers of membrane that were folded into onion-like structures at the nucleoplasmic side of the nuclear envelope. These intranuclear structures did not contain nuclear pores but were positive for the ER proteins calreticulin and protein disulfide isomerase, in addition to abundant DeltaExt/R4Tth. Formation of the intranuclear structures was sensitive to inhibition of protein kinase C. Live microscopy of a green-fluorescent-protein/DeltaExt/R4Tth fusion protein showed that the intranuclear structures were stable and immobile, suggesting that they function as deposits of the overexpressed mutant and associated membrane. The DeltaExt/R4Tth protein also induced formation of densely packed membrane stacks in the cytosol and we suggest a model were the intranuclear structures are formed by invagination of ER-derived membrane stacks into the nucleus.</description><identifier>ISSN: 0021-9533</identifier><identifier>EISSN: 1477-9137</identifier><identifier>DOI: 10.1242/jcs.01047</identifier><identifier>PMID: 15075241</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Cell Membrane - metabolism ; Cell Membrane - ultrastructure ; Cell Nucleus - metabolism ; Cell Nucleus - ultrastructure ; COS Cells ; Indoles - pharmacology ; Intracellular Membranes - metabolism ; Intracellular Membranes - ultrastructure ; Isoquinolines - pharmacology ; Maleimides - pharmacology ; Microscopy, Fluorescence ; Protein Kinase C - antagonists & inhibitors ; Protein Kinase C - metabolism ; Protein Kinases - chemistry ; Protein Kinases - deficiency ; Protein Kinases - genetics ; Protein Kinases - metabolism ; Protein Structure, Tertiary - genetics ; Receptor, Fibroblast Growth Factor, Type 4 ; Receptors, Fibroblast Growth Factor - chemistry ; Receptors, Fibroblast Growth Factor - genetics ; Receptors, Fibroblast Growth Factor - metabolism ; Sequence Deletion - genetics ; Staurosporine - pharmacology ; Sulfonamides - pharmacology</subject><ispartof>Journal of cell science, 2004-04, Vol.117 (Pt 9), p.1807-1819</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-af09dee80f3ef91570b739c4cb3d3492358a23138c6b4f5efdec73feabfeccbb3</citedby><cites>FETCH-LOGICAL-c418t-af09dee80f3ef91570b739c4cb3d3492358a23138c6b4f5efdec73feabfeccbb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3665,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15075241$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sørensen, Vigdis</creatorcontrib><creatorcontrib>Brech, Andreas</creatorcontrib><creatorcontrib>Khnykin, Denis</creatorcontrib><creatorcontrib>Kolpakova, Elona</creatorcontrib><creatorcontrib>Citores, Lucia</creatorcontrib><creatorcontrib>Olsnes, Sjur</creatorcontrib><title>Deletion mutant of FGFR4 induces onion-like membrane structures in the nucleus</title><title>Journal of cell science</title><addtitle>J Cell Sci</addtitle><description>The expression of several deletion mutants of fibroblast growth factor receptor 4 (FGFR4) was studied in COS-1 cells. FGFR4-mutants lacking most of the extracellular region did not efficiently reach the plasma membrane but accumulated in the endoplasmic reticulum (ER) and Golgi body. A mutant FGFR4 lacking the kinase domain as well as most of the extracellular region (DeltaExt/R4Tth) had a distinct intracellular distribution. It localized in part to the nucleus, where it exhibited a striking spotted pattern. Ultrastructural studies showed that the nuclear spots consisted of several layers of membrane that were folded into onion-like structures at the nucleoplasmic side of the nuclear envelope. These intranuclear structures did not contain nuclear pores but were positive for the ER proteins calreticulin and protein disulfide isomerase, in addition to abundant DeltaExt/R4Tth. Formation of the intranuclear structures was sensitive to inhibition of protein kinase C. Live microscopy of a green-fluorescent-protein/DeltaExt/R4Tth fusion protein showed that the intranuclear structures were stable and immobile, suggesting that they function as deposits of the overexpressed mutant and associated membrane. The DeltaExt/R4Tth protein also induced formation of densely packed membrane stacks in the cytosol and we suggest a model were the intranuclear structures are formed by invagination of ER-derived membrane stacks into the nucleus.</description><subject>Animals</subject><subject>Cell Membrane - metabolism</subject><subject>Cell Membrane - ultrastructure</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Nucleus - ultrastructure</subject><subject>COS Cells</subject><subject>Indoles - pharmacology</subject><subject>Intracellular Membranes - metabolism</subject><subject>Intracellular Membranes - ultrastructure</subject><subject>Isoquinolines - pharmacology</subject><subject>Maleimides - pharmacology</subject><subject>Microscopy, Fluorescence</subject><subject>Protein Kinase C - antagonists & inhibitors</subject><subject>Protein Kinase C - metabolism</subject><subject>Protein Kinases - chemistry</subject><subject>Protein Kinases - deficiency</subject><subject>Protein Kinases - genetics</subject><subject>Protein Kinases - metabolism</subject><subject>Protein Structure, Tertiary - genetics</subject><subject>Receptor, Fibroblast Growth Factor, Type 4</subject><subject>Receptors, Fibroblast Growth Factor - chemistry</subject><subject>Receptors, Fibroblast Growth Factor - genetics</subject><subject>Receptors, Fibroblast Growth Factor - metabolism</subject><subject>Sequence Deletion - genetics</subject><subject>Staurosporine - pharmacology</subject><subject>Sulfonamides - pharmacology</subject><issn>0021-9533</issn><issn>1477-9137</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtLAzEURoMotlYX_gHJSnAxNU8zWUprq1AURNdDkrnBqfOoeSz894624OouvsPhchC6pGROmWC3WxfnhBKhjtCUCqUKTbk6RlNCGC205HyCzmLcEkIU0-oUTagkSjJBp-h5CS2kZuhxl5PpEx48Xq1XrwI3fZ0dRDz041q0zSfgDjobTA84ppBdymGcmx6nD8B9di3keI5OvGkjXBzuDL2vHt4Wj8XmZf20uN8UTtAyFcYTXQOUxHPwmkpFrOLaCWd5zYVmXJaGccpLd2eFl-BrcIp7MNaDc9byGbree3dh-MoQU9U10UHbjt8NOVaKlozJUTRDN3vQhSHGAL7ahaYz4buipPqNV43xqr94I3t1kGbbQf1PHmrxH6jNa1k</recordid><startdate>20040401</startdate><enddate>20040401</enddate><creator>Sørensen, Vigdis</creator><creator>Brech, Andreas</creator><creator>Khnykin, Denis</creator><creator>Kolpakova, Elona</creator><creator>Citores, Lucia</creator><creator>Olsnes, Sjur</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></search><sort><creationdate>20040401</creationdate><title>Deletion mutant of FGFR4 induces onion-like membrane structures in the nucleus</title><author>Sørensen, Vigdis ; Brech, Andreas ; Khnykin, Denis ; Kolpakova, Elona ; Citores, Lucia ; Olsnes, Sjur</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-af09dee80f3ef91570b739c4cb3d3492358a23138c6b4f5efdec73feabfeccbb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Cell Membrane - metabolism</topic><topic>Cell Membrane - ultrastructure</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell Nucleus - ultrastructure</topic><topic>COS Cells</topic><topic>Indoles - pharmacology</topic><topic>Intracellular Membranes - metabolism</topic><topic>Intracellular Membranes - ultrastructure</topic><topic>Isoquinolines - pharmacology</topic><topic>Maleimides - pharmacology</topic><topic>Microscopy, Fluorescence</topic><topic>Protein Kinase C - antagonists & inhibitors</topic><topic>Protein Kinase C - metabolism</topic><topic>Protein Kinases - chemistry</topic><topic>Protein Kinases - deficiency</topic><topic>Protein Kinases - genetics</topic><topic>Protein Kinases - metabolism</topic><topic>Protein Structure, Tertiary - genetics</topic><topic>Receptor, Fibroblast Growth Factor, Type 4</topic><topic>Receptors, Fibroblast Growth Factor - chemistry</topic><topic>Receptors, Fibroblast Growth Factor - genetics</topic><topic>Receptors, Fibroblast Growth Factor - metabolism</topic><topic>Sequence Deletion - genetics</topic><topic>Staurosporine - pharmacology</topic><topic>Sulfonamides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sørensen, Vigdis</creatorcontrib><creatorcontrib>Brech, Andreas</creatorcontrib><creatorcontrib>Khnykin, Denis</creatorcontrib><creatorcontrib>Kolpakova, Elona</creatorcontrib><creatorcontrib>Citores, Lucia</creatorcontrib><creatorcontrib>Olsnes, Sjur</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>Journal of cell science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sørensen, Vigdis</au><au>Brech, Andreas</au><au>Khnykin, Denis</au><au>Kolpakova, Elona</au><au>Citores, Lucia</au><au>Olsnes, Sjur</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deletion mutant of FGFR4 induces onion-like membrane structures in the nucleus</atitle><jtitle>Journal of cell science</jtitle><addtitle>J Cell Sci</addtitle><date>2004-04-01</date><risdate>2004</risdate><volume>117</volume><issue>Pt 9</issue><spage>1807</spage><epage>1819</epage><pages>1807-1819</pages><issn>0021-9533</issn><eissn>1477-9137</eissn><abstract>The expression of several deletion mutants of fibroblast growth factor receptor 4 (FGFR4) was studied in COS-1 cells. FGFR4-mutants lacking most of the extracellular region did not efficiently reach the plasma membrane but accumulated in the endoplasmic reticulum (ER) and Golgi body. A mutant FGFR4 lacking the kinase domain as well as most of the extracellular region (DeltaExt/R4Tth) had a distinct intracellular distribution. It localized in part to the nucleus, where it exhibited a striking spotted pattern. Ultrastructural studies showed that the nuclear spots consisted of several layers of membrane that were folded into onion-like structures at the nucleoplasmic side of the nuclear envelope. These intranuclear structures did not contain nuclear pores but were positive for the ER proteins calreticulin and protein disulfide isomerase, in addition to abundant DeltaExt/R4Tth. Formation of the intranuclear structures was sensitive to inhibition of protein kinase C. Live microscopy of a green-fluorescent-protein/DeltaExt/R4Tth fusion protein showed that the intranuclear structures were stable and immobile, suggesting that they function as deposits of the overexpressed mutant and associated membrane. The DeltaExt/R4Tth protein also induced formation of densely packed membrane stacks in the cytosol and we suggest a model were the intranuclear structures are formed by invagination of ER-derived membrane stacks into the nucleus.</abstract><cop>England</cop><pmid>15075241</pmid><doi>10.1242/jcs.01047</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Cell Membrane - metabolism Cell Membrane - ultrastructure Cell Nucleus - metabolism Cell Nucleus - ultrastructure COS Cells Indoles - pharmacology Intracellular Membranes - metabolism Intracellular Membranes - ultrastructure Isoquinolines - pharmacology Maleimides - pharmacology Microscopy, Fluorescence Protein Kinase C - antagonists & inhibitors Protein Kinase C - metabolism Protein Kinases - chemistry Protein Kinases - deficiency Protein Kinases - genetics Protein Kinases - metabolism Protein Structure, Tertiary - genetics Receptor, Fibroblast Growth Factor, Type 4 Receptors, Fibroblast Growth Factor - chemistry Receptors, Fibroblast Growth Factor - genetics Receptors, Fibroblast Growth Factor - metabolism Sequence Deletion - genetics Staurosporine - pharmacology Sulfonamides - pharmacology |
title | Deletion mutant of FGFR4 induces onion-like membrane structures in the nucleus |
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