Mechanism of exportin retention in the cell nucleus
Exportin receptors are concentrated in the nucleus to transport essential cargoes out of it. A mislocalization of exportins to the cytoplasm is linked to disease. Hence, it is important to understand how their containment within the nucleus is regulated. Here, we have studied the nuclear efflux of e...
Gespeichert in:
| Veröffentlicht in: | The Journal of cell biology 2024-02, Vol.223 (2), p.1 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 2 |
| container_start_page | 1 |
| container_title | The Journal of cell biology |
| container_volume | 223 |
| creator | Kapinos, Larisa E Kalita, Joanna Kassianidou, Elena Rencurel, Chantal Lim, Roderick Y H |
| description | Exportin receptors are concentrated in the nucleus to transport essential cargoes out of it. A mislocalization of exportins to the cytoplasm is linked to disease. Hence, it is important to understand how their containment within the nucleus is regulated. Here, we have studied the nuclear efflux of exportin2 (cellular apoptosis susceptibility protein or CAS) that delivers karyopherinα (Kapα or importinα), the cargo adaptor for karyopherinβ1 (Kapβ1 or importinβ1), to the cytoplasm in a Ran guanosine triphosphate (RanGTP)-mediated manner. We show that the N-terminus of CAS attenuates the interaction of RanGTPase activating protein 1 (RanGAP1) with RanGTP to slow GTP hydrolysis, which suppresses CAS nuclear exit at nuclear pore complexes (NPCs). Strikingly, a single phosphomimetic mutation (T18D) at the CAS N-terminus is sufficient to abolish its nuclear retention and coincides with metastatic cellular behavior. Furthermore, downregulating Kapβ1 disrupts CAS nuclear retention, which highlights the balance between their respective functions that is essential for maintaining the Kapα transport cycle. Therefore, NPCs play a functional role in selectively partitioning exportins in the cell nucleus. |
| doi_str_mv | 10.1083/jcb.202306094 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10798875</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2921195886</sourcerecordid><originalsourceid>FETCH-LOGICAL-c416t-117c1aa4ff5d44d2701a4f971b586b952355e3d6be0882b9cfeafa35796675ad3</originalsourceid><addsrcrecordid>eNpdkc1rGzEUxEVIiR0nx1zDQi65bPqePlbSqRSTNgWXXpKz0Gq19Zr1ypF2S_rfV8auSXt6DO_HMMMQcoPwgKDYx42rHyhQBhVofkbmKDiUCjmckzkAxVILKmbkMqUNAHDJ2QWZMUU5Auo5Yd-9W9uhS9sitIV_24U4dkMR_eiHsQtDkcW49oXzfV8Mk-v9lK7Ih9b2yV8f74K8fHl8Xj6Vqx9fvy0_r0rHsRpLROnQWt62ouG8oRIwCy2xFqqqcywmhGdNVXtQitbatd62lgmpq0oK27AF-XTw3U311jcuJ4q2N7vYbW38bYLtzL-foVubn-GXQZBaKSmyw_3RIYbXyafRbLu0r2IHH6ZkqEYpBEdOM3r3H7oJUxxyv0xRRC2UqjJVHigXQ0rRt6c0CGa_h8l7mNMemb99X-FE_x2A_QHtb4Vd</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2921195886</pqid></control><display><type>article</type><title>Mechanism of exportin retention in the cell nucleus</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Kapinos, Larisa E ; Kalita, Joanna ; Kassianidou, Elena ; Rencurel, Chantal ; Lim, Roderick Y H</creator><creatorcontrib>Kapinos, Larisa E ; Kalita, Joanna ; Kassianidou, Elena ; Rencurel, Chantal ; Lim, Roderick Y H</creatorcontrib><description>Exportin receptors are concentrated in the nucleus to transport essential cargoes out of it. A mislocalization of exportins to the cytoplasm is linked to disease. Hence, it is important to understand how their containment within the nucleus is regulated. Here, we have studied the nuclear efflux of exportin2 (cellular apoptosis susceptibility protein or CAS) that delivers karyopherinα (Kapα or importinα), the cargo adaptor for karyopherinβ1 (Kapβ1 or importinβ1), to the cytoplasm in a Ran guanosine triphosphate (RanGTP)-mediated manner. We show that the N-terminus of CAS attenuates the interaction of RanGTPase activating protein 1 (RanGAP1) with RanGTP to slow GTP hydrolysis, which suppresses CAS nuclear exit at nuclear pore complexes (NPCs). Strikingly, a single phosphomimetic mutation (T18D) at the CAS N-terminus is sufficient to abolish its nuclear retention and coincides with metastatic cellular behavior. Furthermore, downregulating Kapβ1 disrupts CAS nuclear retention, which highlights the balance between their respective functions that is essential for maintaining the Kapα transport cycle. Therefore, NPCs play a functional role in selectively partitioning exportins in the cell nucleus.</description><identifier>ISSN: 0021-9525</identifier><identifier>ISSN: 1540-8140</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.202306094</identifier><identifier>PMID: 38241019</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Active Transport, Cell Nucleus - physiology ; Adaptor proteins ; Apoptosis ; Biochemistry ; Biological Transport ; Cancer ; Cell Nucleus - metabolism ; Cellular apoptosis susceptibility protein ; Cellular Apoptosis Susceptibility Protein - genetics ; Cellular Apoptosis Susceptibility Protein - metabolism ; Cytoplasm ; Cytoplasm - metabolism ; Efflux ; Humans ; Karyopherins - metabolism ; Metastases ; N-Terminus ; Nuclear Pore - metabolism ; Nuclear pores ; Nuclei (cytology) ; Protein Homeostasis ; Proteins ; ran GTP-Binding Protein - metabolism ; Retention ; Trafficking</subject><ispartof>The Journal of cell biology, 2024-02, Vol.223 (2), p.1</ispartof><rights>2024 Kapinos et al.</rights><rights>Copyright Rockefeller University Press Feb 2024</rights><rights>2024 Kapinos et al. 2024 Kapinos et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-117c1aa4ff5d44d2701a4f971b586b952355e3d6be0882b9cfeafa35796675ad3</citedby><cites>FETCH-LOGICAL-c416t-117c1aa4ff5d44d2701a4f971b586b952355e3d6be0882b9cfeafa35796675ad3</cites><orcidid>0000-0001-6101-0876 ; 0000-0001-5015-6087 ; 0000-0002-5854-0072 ; 0009-0008-8562-7211 ; 0009-0009-8798-915X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38241019$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kapinos, Larisa E</creatorcontrib><creatorcontrib>Kalita, Joanna</creatorcontrib><creatorcontrib>Kassianidou, Elena</creatorcontrib><creatorcontrib>Rencurel, Chantal</creatorcontrib><creatorcontrib>Lim, Roderick Y H</creatorcontrib><title>Mechanism of exportin retention in the cell nucleus</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>Exportin receptors are concentrated in the nucleus to transport essential cargoes out of it. A mislocalization of exportins to the cytoplasm is linked to disease. Hence, it is important to understand how their containment within the nucleus is regulated. Here, we have studied the nuclear efflux of exportin2 (cellular apoptosis susceptibility protein or CAS) that delivers karyopherinα (Kapα or importinα), the cargo adaptor for karyopherinβ1 (Kapβ1 or importinβ1), to the cytoplasm in a Ran guanosine triphosphate (RanGTP)-mediated manner. We show that the N-terminus of CAS attenuates the interaction of RanGTPase activating protein 1 (RanGAP1) with RanGTP to slow GTP hydrolysis, which suppresses CAS nuclear exit at nuclear pore complexes (NPCs). Strikingly, a single phosphomimetic mutation (T18D) at the CAS N-terminus is sufficient to abolish its nuclear retention and coincides with metastatic cellular behavior. Furthermore, downregulating Kapβ1 disrupts CAS nuclear retention, which highlights the balance between their respective functions that is essential for maintaining the Kapα transport cycle. Therefore, NPCs play a functional role in selectively partitioning exportins in the cell nucleus.</description><subject>Active Transport, Cell Nucleus - physiology</subject><subject>Adaptor proteins</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biological Transport</subject><subject>Cancer</subject><subject>Cell Nucleus - metabolism</subject><subject>Cellular apoptosis susceptibility protein</subject><subject>Cellular Apoptosis Susceptibility Protein - genetics</subject><subject>Cellular Apoptosis Susceptibility Protein - metabolism</subject><subject>Cytoplasm</subject><subject>Cytoplasm - metabolism</subject><subject>Efflux</subject><subject>Humans</subject><subject>Karyopherins - metabolism</subject><subject>Metastases</subject><subject>N-Terminus</subject><subject>Nuclear Pore - metabolism</subject><subject>Nuclear pores</subject><subject>Nuclei (cytology)</subject><subject>Protein Homeostasis</subject><subject>Proteins</subject><subject>ran GTP-Binding Protein - metabolism</subject><subject>Retention</subject><subject>Trafficking</subject><issn>0021-9525</issn><issn>1540-8140</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1rGzEUxEVIiR0nx1zDQi65bPqePlbSqRSTNgWXXpKz0Gq19Zr1ypF2S_rfV8auSXt6DO_HMMMQcoPwgKDYx42rHyhQBhVofkbmKDiUCjmckzkAxVILKmbkMqUNAHDJ2QWZMUU5Auo5Yd-9W9uhS9sitIV_24U4dkMR_eiHsQtDkcW49oXzfV8Mk-v9lK7Ih9b2yV8f74K8fHl8Xj6Vqx9fvy0_r0rHsRpLROnQWt62ouG8oRIwCy2xFqqqcywmhGdNVXtQitbatd62lgmpq0oK27AF-XTw3U311jcuJ4q2N7vYbW38bYLtzL-foVubn-GXQZBaKSmyw_3RIYbXyafRbLu0r2IHH6ZkqEYpBEdOM3r3H7oJUxxyv0xRRC2UqjJVHigXQ0rRt6c0CGa_h8l7mNMemb99X-FE_x2A_QHtb4Vd</recordid><startdate>20240205</startdate><enddate>20240205</enddate><creator>Kapinos, Larisa E</creator><creator>Kalita, Joanna</creator><creator>Kassianidou, Elena</creator><creator>Rencurel, Chantal</creator><creator>Lim, Roderick Y H</creator><general>Rockefeller University Press</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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6101-0876</orcidid><orcidid>https://orcid.org/0000-0001-5015-6087</orcidid><orcidid>https://orcid.org/0000-0002-5854-0072</orcidid><orcidid>https://orcid.org/0009-0008-8562-7211</orcidid><orcidid>https://orcid.org/0009-0009-8798-915X</orcidid></search><sort><creationdate>20240205</creationdate><title>Mechanism of exportin retention in the cell nucleus</title><author>Kapinos, Larisa E ; Kalita, Joanna ; Kassianidou, Elena ; Rencurel, Chantal ; Lim, Roderick Y H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-117c1aa4ff5d44d2701a4f971b586b952355e3d6be0882b9cfeafa35796675ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Active Transport, Cell Nucleus - physiology</topic><topic>Adaptor proteins</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biological Transport</topic><topic>Cancer</topic><topic>Cell Nucleus - metabolism</topic><topic>Cellular apoptosis susceptibility protein</topic><topic>Cellular Apoptosis Susceptibility Protein - genetics</topic><topic>Cellular Apoptosis Susceptibility Protein - metabolism</topic><topic>Cytoplasm</topic><topic>Cytoplasm - metabolism</topic><topic>Efflux</topic><topic>Humans</topic><topic>Karyopherins - metabolism</topic><topic>Metastases</topic><topic>N-Terminus</topic><topic>Nuclear Pore - metabolism</topic><topic>Nuclear pores</topic><topic>Nuclei (cytology)</topic><topic>Protein Homeostasis</topic><topic>Proteins</topic><topic>ran GTP-Binding Protein - metabolism</topic><topic>Retention</topic><topic>Trafficking</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kapinos, Larisa E</creatorcontrib><creatorcontrib>Kalita, Joanna</creatorcontrib><creatorcontrib>Kassianidou, Elena</creatorcontrib><creatorcontrib>Rencurel, Chantal</creatorcontrib><creatorcontrib>Lim, Roderick Y H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kapinos, Larisa E</au><au>Kalita, Joanna</au><au>Kassianidou, Elena</au><au>Rencurel, Chantal</au><au>Lim, Roderick Y H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanism of exportin retention in the cell nucleus</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>2024-02-05</date><risdate>2024</risdate><volume>223</volume><issue>2</issue><spage>1</spage><pages>1-</pages><issn>0021-9525</issn><issn>1540-8140</issn><eissn>1540-8140</eissn><abstract>Exportin receptors are concentrated in the nucleus to transport essential cargoes out of it. A mislocalization of exportins to the cytoplasm is linked to disease. Hence, it is important to understand how their containment within the nucleus is regulated. Here, we have studied the nuclear efflux of exportin2 (cellular apoptosis susceptibility protein or CAS) that delivers karyopherinα (Kapα or importinα), the cargo adaptor for karyopherinβ1 (Kapβ1 or importinβ1), to the cytoplasm in a Ran guanosine triphosphate (RanGTP)-mediated manner. We show that the N-terminus of CAS attenuates the interaction of RanGTPase activating protein 1 (RanGAP1) with RanGTP to slow GTP hydrolysis, which suppresses CAS nuclear exit at nuclear pore complexes (NPCs). Strikingly, a single phosphomimetic mutation (T18D) at the CAS N-terminus is sufficient to abolish its nuclear retention and coincides with metastatic cellular behavior. Furthermore, downregulating Kapβ1 disrupts CAS nuclear retention, which highlights the balance between their respective functions that is essential for maintaining the Kapα transport cycle. Therefore, NPCs play a functional role in selectively partitioning exportins in the cell nucleus.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>38241019</pmid><doi>10.1083/jcb.202306094</doi><orcidid>https://orcid.org/0000-0001-6101-0876</orcidid><orcidid>https://orcid.org/0000-0001-5015-6087</orcidid><orcidid>https://orcid.org/0000-0002-5854-0072</orcidid><orcidid>https://orcid.org/0009-0008-8562-7211</orcidid><orcidid>https://orcid.org/0009-0009-8798-915X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9525 |
| ispartof | The Journal of cell biology, 2024-02, Vol.223 (2), p.1 |
| issn | 0021-9525 1540-8140 1540-8140 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10798875 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Active Transport, Cell Nucleus - physiology Adaptor proteins Apoptosis Biochemistry Biological Transport Cancer Cell Nucleus - metabolism Cellular apoptosis susceptibility protein Cellular Apoptosis Susceptibility Protein - genetics Cellular Apoptosis Susceptibility Protein - metabolism Cytoplasm Cytoplasm - metabolism Efflux Humans Karyopherins - metabolism Metastases N-Terminus Nuclear Pore - metabolism Nuclear pores Nuclei (cytology) Protein Homeostasis Proteins ran GTP-Binding Protein - metabolism Retention Trafficking |
| title | Mechanism of exportin retention in the cell nucleus |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T23%3A14%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mechanism%20of%20exportin%20retention%20in%20the%20cell%20nucleus&rft.jtitle=The%20Journal%20of%20cell%20biology&rft.au=Kapinos,%20Larisa%20E&rft.date=2024-02-05&rft.volume=223&rft.issue=2&rft.spage=1&rft.pages=1-&rft.issn=0021-9525&rft.eissn=1540-8140&rft_id=info:doi/10.1083/jcb.202306094&rft_dat=%3Cproquest_pubme%3E2921195886%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2921195886&rft_id=info:pmid/38241019&rfr_iscdi=true |