Rabgap1 promotes recycling of active β1 integrins to support effective cell migration
Integrin function depends on the continuous internalization of integrins and their subsequent endosomal recycling to the plasma membrane to drive adhesion dynamics, cell migration and invasion. Here we assign a pivotal role for Rabgap1 (GAPCenA) in the recycling of endocytosed active β1 integrins to...
Gespeichert in:
| Veröffentlicht in: | Journal of cell science 2020-09, Vol.133 (18) |
|---|---|
| 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 | 18 |
| container_start_page | |
| container_title | Journal of cell science |
| container_volume | 133 |
| creator | Samarelli, Anna V Ziegler, Tilman Meves, Alexander Fässler, Reinhard Böttcher, Ralph T |
| description | Integrin function depends on the continuous internalization of integrins and their subsequent endosomal recycling to the plasma membrane to drive adhesion dynamics, cell migration and invasion. Here we assign a pivotal role for Rabgap1 (GAPCenA) in the recycling of endocytosed active β1 integrins to the plasma membrane. The phosphotyrosine-binding (PTB) domain of Rabgap1 binds to the membrane-proximal NPxY motif in the cytoplasmic domain of β1 integrin subunits on endosomes. Silencing Rabgap1 in mouse fibroblasts leads to the intracellular accumulation of active β1 integrins, alters focal adhesion formation, and decreases cell migration and cancer cell invasion. Functionally, Rabgap1 facilitates active β1 integrin recycling to the plasma membrane through attenuation of Rab11 activity. Taken together, our results identify Rabgap1 as an important factor for conformation-specific integrin trafficking and define the role of Rabgap1 in β1-integrin-mediated cell migration in mouse fibroblasts and breast cancer cells. |
| doi_str_mv | 10.1242/jcs.243683 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7522031</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2437400365</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2933-1bf33c4204d0a7a2b6520aa17d11ee4157b4a3e52d72de1ff03584445e49439b3</originalsourceid><addsrcrecordid>eNpVkd1KxDAQhYMo7vpz4wNILkWoJplks70RZPEPBEHU25Cm0xppm5p0BV_LB_GZrOwqejUX83HOzDmEHHB2woUUpy8unQgJszlskCmXWmc5B71JpowJnuUKYEJ2UnphjGmR620yATGXoLSckqd7W9S257SPoQ0DJhrRvbvGdzUNFbVu8G9IPz849d2AdfRdokOgadn3IQ4UqwpXiMOmoa2vox186PbIVmWbhPvruUseLy8eFtfZ7d3VzeL8NnMiB8h4UQE4KZgsmdVWFDMlmLVcl5wjSq50IS2gEqUWJfKqYqDmUkqFMpeQF7BLzla6_bJosXTYDdE2po--tfHdBOvN_03nn00d3oxWQjDgo8DRWiCG1yWmwbQ-ff9iOwzLZMZctWQMZmpEj1eoiyGliNWvDWfmuwgzFmFWRYzw4d_DftGf5OELvSmFfQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2437400365</pqid></control><display><type>article</type><title>Rabgap1 promotes recycling of active β1 integrins to support effective cell migration</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><source>Company of Biologists</source><creator>Samarelli, Anna V ; Ziegler, Tilman ; Meves, Alexander ; Fässler, Reinhard ; Böttcher, Ralph T</creator><creatorcontrib>Samarelli, Anna V ; Ziegler, Tilman ; Meves, Alexander ; Fässler, Reinhard ; Böttcher, Ralph T</creatorcontrib><description>Integrin function depends on the continuous internalization of integrins and their subsequent endosomal recycling to the plasma membrane to drive adhesion dynamics, cell migration and invasion. Here we assign a pivotal role for Rabgap1 (GAPCenA) in the recycling of endocytosed active β1 integrins to the plasma membrane. The phosphotyrosine-binding (PTB) domain of Rabgap1 binds to the membrane-proximal NPxY motif in the cytoplasmic domain of β1 integrin subunits on endosomes. Silencing Rabgap1 in mouse fibroblasts leads to the intracellular accumulation of active β1 integrins, alters focal adhesion formation, and decreases cell migration and cancer cell invasion. Functionally, Rabgap1 facilitates active β1 integrin recycling to the plasma membrane through attenuation of Rab11 activity. Taken together, our results identify Rabgap1 as an important factor for conformation-specific integrin trafficking and define the role of Rabgap1 in β1-integrin-mediated cell migration in mouse fibroblasts and breast cancer cells.</description><identifier>ISSN: 0021-9533</identifier><identifier>EISSN: 1477-9137</identifier><identifier>DOI: 10.1242/jcs.243683</identifier><identifier>PMID: 32843574</identifier><language>eng</language><publisher>England: The Company of Biologists Ltd</publisher><subject>Animals ; Cell Adhesion ; Cell Membrane ; Cell Movement ; Endosomes ; GTPase-Activating Proteins ; Integrin beta1 - genetics ; Integrins ; Mice ; Microtubule-Associated Proteins</subject><ispartof>Journal of cell science, 2020-09, Vol.133 (18)</ispartof><rights>2020. Published by The Company of Biologists Ltd.</rights><rights>2020. Published by The Company of Biologists Ltd 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2933-1bf33c4204d0a7a2b6520aa17d11ee4157b4a3e52d72de1ff03584445e49439b3</citedby><cites>FETCH-LOGICAL-c2933-1bf33c4204d0a7a2b6520aa17d11ee4157b4a3e52d72de1ff03584445e49439b3</cites><orcidid>0000-0003-3050-7163 ; 0000-0001-7462-8288</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3678,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32843574$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Samarelli, Anna V</creatorcontrib><creatorcontrib>Ziegler, Tilman</creatorcontrib><creatorcontrib>Meves, Alexander</creatorcontrib><creatorcontrib>Fässler, Reinhard</creatorcontrib><creatorcontrib>Böttcher, Ralph T</creatorcontrib><title>Rabgap1 promotes recycling of active β1 integrins to support effective cell migration</title><title>Journal of cell science</title><addtitle>J Cell Sci</addtitle><description>Integrin function depends on the continuous internalization of integrins and their subsequent endosomal recycling to the plasma membrane to drive adhesion dynamics, cell migration and invasion. Here we assign a pivotal role for Rabgap1 (GAPCenA) in the recycling of endocytosed active β1 integrins to the plasma membrane. The phosphotyrosine-binding (PTB) domain of Rabgap1 binds to the membrane-proximal NPxY motif in the cytoplasmic domain of β1 integrin subunits on endosomes. Silencing Rabgap1 in mouse fibroblasts leads to the intracellular accumulation of active β1 integrins, alters focal adhesion formation, and decreases cell migration and cancer cell invasion. Functionally, Rabgap1 facilitates active β1 integrin recycling to the plasma membrane through attenuation of Rab11 activity. Taken together, our results identify Rabgap1 as an important factor for conformation-specific integrin trafficking and define the role of Rabgap1 in β1-integrin-mediated cell migration in mouse fibroblasts and breast cancer cells.</description><subject>Animals</subject><subject>Cell Adhesion</subject><subject>Cell Membrane</subject><subject>Cell Movement</subject><subject>Endosomes</subject><subject>GTPase-Activating Proteins</subject><subject>Integrin beta1 - genetics</subject><subject>Integrins</subject><subject>Mice</subject><subject>Microtubule-Associated Proteins</subject><issn>0021-9533</issn><issn>1477-9137</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkd1KxDAQhYMo7vpz4wNILkWoJplks70RZPEPBEHU25Cm0xppm5p0BV_LB_GZrOwqejUX83HOzDmEHHB2woUUpy8unQgJszlskCmXWmc5B71JpowJnuUKYEJ2UnphjGmR620yATGXoLSckqd7W9S257SPoQ0DJhrRvbvGdzUNFbVu8G9IPz849d2AdfRdokOgadn3IQ4UqwpXiMOmoa2vox186PbIVmWbhPvruUseLy8eFtfZ7d3VzeL8NnMiB8h4UQE4KZgsmdVWFDMlmLVcl5wjSq50IS2gEqUWJfKqYqDmUkqFMpeQF7BLzla6_bJosXTYDdE2po--tfHdBOvN_03nn00d3oxWQjDgo8DRWiCG1yWmwbQ-ff9iOwzLZMZctWQMZmpEj1eoiyGliNWvDWfmuwgzFmFWRYzw4d_DftGf5OELvSmFfQ</recordid><startdate>20200923</startdate><enddate>20200923</enddate><creator>Samarelli, Anna V</creator><creator>Ziegler, Tilman</creator><creator>Meves, Alexander</creator><creator>Fässler, Reinhard</creator><creator>Böttcher, Ralph T</creator><general>The Company of Biologists Ltd</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>5PM</scope><orcidid>https://orcid.org/0000-0003-3050-7163</orcidid><orcidid>https://orcid.org/0000-0001-7462-8288</orcidid></search><sort><creationdate>20200923</creationdate><title>Rabgap1 promotes recycling of active β1 integrins to support effective cell migration</title><author>Samarelli, Anna V ; Ziegler, Tilman ; Meves, Alexander ; Fässler, Reinhard ; Böttcher, Ralph T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2933-1bf33c4204d0a7a2b6520aa17d11ee4157b4a3e52d72de1ff03584445e49439b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Cell Adhesion</topic><topic>Cell Membrane</topic><topic>Cell Movement</topic><topic>Endosomes</topic><topic>GTPase-Activating Proteins</topic><topic>Integrin beta1 - genetics</topic><topic>Integrins</topic><topic>Mice</topic><topic>Microtubule-Associated Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Samarelli, Anna V</creatorcontrib><creatorcontrib>Ziegler, Tilman</creatorcontrib><creatorcontrib>Meves, Alexander</creatorcontrib><creatorcontrib>Fässler, Reinhard</creatorcontrib><creatorcontrib>Böttcher, Ralph T</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>Journal of cell science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Samarelli, Anna V</au><au>Ziegler, Tilman</au><au>Meves, Alexander</au><au>Fässler, Reinhard</au><au>Böttcher, Ralph T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rabgap1 promotes recycling of active β1 integrins to support effective cell migration</atitle><jtitle>Journal of cell science</jtitle><addtitle>J Cell Sci</addtitle><date>2020-09-23</date><risdate>2020</risdate><volume>133</volume><issue>18</issue><issn>0021-9533</issn><eissn>1477-9137</eissn><abstract>Integrin function depends on the continuous internalization of integrins and their subsequent endosomal recycling to the plasma membrane to drive adhesion dynamics, cell migration and invasion. Here we assign a pivotal role for Rabgap1 (GAPCenA) in the recycling of endocytosed active β1 integrins to the plasma membrane. The phosphotyrosine-binding (PTB) domain of Rabgap1 binds to the membrane-proximal NPxY motif in the cytoplasmic domain of β1 integrin subunits on endosomes. Silencing Rabgap1 in mouse fibroblasts leads to the intracellular accumulation of active β1 integrins, alters focal adhesion formation, and decreases cell migration and cancer cell invasion. Functionally, Rabgap1 facilitates active β1 integrin recycling to the plasma membrane through attenuation of Rab11 activity. Taken together, our results identify Rabgap1 as an important factor for conformation-specific integrin trafficking and define the role of Rabgap1 in β1-integrin-mediated cell migration in mouse fibroblasts and breast cancer cells.</abstract><cop>England</cop><pub>The Company of Biologists Ltd</pub><pmid>32843574</pmid><doi>10.1242/jcs.243683</doi><orcidid>https://orcid.org/0000-0003-3050-7163</orcidid><orcidid>https://orcid.org/0000-0001-7462-8288</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9533 |
| ispartof | Journal of cell science, 2020-09, Vol.133 (18) |
| issn | 0021-9533 1477-9137 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7522031 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Company of Biologists |
| subjects | Animals Cell Adhesion Cell Membrane Cell Movement Endosomes GTPase-Activating Proteins Integrin beta1 - genetics Integrins Mice Microtubule-Associated Proteins |
| title | Rabgap1 promotes recycling of active β1 integrins to support effective cell migration |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T15%3A00%3A19IST&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=Rabgap1%20promotes%20recycling%20of%20active%20%CE%B21%20integrins%20to%20support%20effective%20cell%20migration&rft.jtitle=Journal%20of%20cell%20science&rft.au=Samarelli,%20Anna%20V&rft.date=2020-09-23&rft.volume=133&rft.issue=18&rft.issn=0021-9533&rft.eissn=1477-9137&rft_id=info:doi/10.1242/jcs.243683&rft_dat=%3Cproquest_pubme%3E2437400365%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=2437400365&rft_id=info:pmid/32843574&rfr_iscdi=true |