Plexin-B1 Directly Interacts with PDZ-RhoGEF/LARG to Regulate RhoA and Growth Cone Morphology
Plexins are widely expressed transmembrane proteins that, in the nervous system, mediate repulsive signals of semaphorins. However, the molecular nature of plexin-mediated signal transduction remains poorly understood. Here, we demonstrate that plexin-B family members associate through their C termi...
Gespeichert in:
| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2002-07, Vol.35 (1), p.51-63 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 63 |
|---|---|
| container_issue | 1 |
| container_start_page | 51 |
| container_title | Neuron (Cambridge, Mass.) |
| container_volume | 35 |
| creator | Swiercz, Jakub M. Kuner, Rohini Behrens, Jürgen Offermanns, Stefan |
| description | Plexins are widely expressed transmembrane proteins that, in the nervous system, mediate repulsive signals of semaphorins. However, the molecular nature of plexin-mediated signal transduction remains poorly understood. Here, we demonstrate that plexin-B family members associate through their C termini with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. Activation of plexin-B1 by semaphorin 4D regulates PDZ-RhoGEF/LARG activity leading to RhoA activation. In addition, a dominant-negative form of PDZ-RhoGEF blocks semaphorin 4D-induced growth cone collapse in primary hippocampal neurons. Our study indicates that the interaction of mammalian plexin-B family members with the multidomain proteins PDZ-RhoGEF and LARG represents an essential molecular link between plexin-B and localized, Rho-mediated downstream signaling events which underly various plexin-mediated cellular phenomena including axonal growth cone collapse. |
| doi_str_mv | 10.1016/S0896-6273(02)00750-X |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71921923</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S089662730200750X</els_id><sourcerecordid>18467282</sourcerecordid><originalsourceid>FETCH-LOGICAL-c519t-cdab93d9fa16a127147ed72c054b2c8e7dd79cb9d87fac3fc3c70e39cee12d263</originalsourceid><addsrcrecordid>eNqFkV1rFDEUhoModlv9CUpAEL0Ym5PMJJOrsm7btbBiWRWKICGbnOlOmZ2syUzr_ntnP1DwpnAgcHjeNyQPIa-AfQAG8vQrK7XMJFfiHePvGVMFy26ekBEwrbIctH5KRn-RI3Kc0h1jkBcanpMj4MCFZOWI_Lxu8HfdZh-BntcRXdds6FXbYbSuS_Sh7pb0-vxHNl-G6cXl6Ww8n9Iu0Dne9o3tkA77MbWtp9MYHgZ2Elqkn0NcL0MTbjcvyLPKNglfHs4T8v3y4tvkUzb7Mr2ajGeZK0B3mfN2oYXXlQVpgSvIFXrFHSvyBXclKu-VdgvtS1VZJyonnGIotEME7rkUJ-Ttvncdw68eU2dWdXLYNLbF0CejQPNhxKMglLlUvOQD-OY_8C70sR0eYaBgQkmh5bau2FMuhpQiVmYd65WNGwPMbDWZnSazdWAYNztN5mbIvT6094sV-n-pg5cBONsDOPzafY3RJFdj69DvJBkf6keu-ANx26B8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1503763963</pqid></control><display><type>article</type><title>Plexin-B1 Directly Interacts with PDZ-RhoGEF/LARG to Regulate RhoA and Growth Cone Morphology</title><source>MEDLINE</source><source>Cell Press Free Archives</source><source>Elsevier ScienceDirect Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Swiercz, Jakub M. ; Kuner, Rohini ; Behrens, Jürgen ; Offermanns, Stefan</creator><creatorcontrib>Swiercz, Jakub M. ; Kuner, Rohini ; Behrens, Jürgen ; Offermanns, Stefan</creatorcontrib><description>Plexins are widely expressed transmembrane proteins that, in the nervous system, mediate repulsive signals of semaphorins. However, the molecular nature of plexin-mediated signal transduction remains poorly understood. Here, we demonstrate that plexin-B family members associate through their C termini with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. Activation of plexin-B1 by semaphorin 4D regulates PDZ-RhoGEF/LARG activity leading to RhoA activation. In addition, a dominant-negative form of PDZ-RhoGEF blocks semaphorin 4D-induced growth cone collapse in primary hippocampal neurons. Our study indicates that the interaction of mammalian plexin-B family members with the multidomain proteins PDZ-RhoGEF and LARG represents an essential molecular link between plexin-B and localized, Rho-mediated downstream signaling events which underly various plexin-mediated cellular phenomena including axonal growth cone collapse.</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/S0896-6273(02)00750-X</identifier><identifier>PMID: 12123608</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Antigens, CD ; Cell Communication - genetics ; Cell Differentiation - genetics ; Cell Membrane - metabolism ; Cells, Cultured ; Chick Embryo ; Cytoskeleton ; Digital cameras ; Fetus ; Growth Cones - metabolism ; Growth Cones - ultrastructure ; Guanine Nucleotide Exchange Factors - genetics ; Guanine Nucleotide Exchange Factors - metabolism ; Hippocampus - embryology ; Hippocampus - growth & development ; Hippocampus - metabolism ; Humans ; Immunohistochemistry ; Insects ; Ligands ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - metabolism ; Mutation - genetics ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Protein Binding - genetics ; Protein Structure, Tertiary - genetics ; Proteins ; Rats ; Receptors, Cell Surface - genetics ; Receptors, Cell Surface - metabolism ; Regulation ; Retinal Ganglion Cells - cytology ; Retinal Ganglion Cells - metabolism ; Rho Guanine Nucleotide Exchange Factors ; rhoA GTP-Binding Protein - genetics ; rhoA GTP-Binding Protein - metabolism ; Semaphorins ; Signal Transduction - genetics</subject><ispartof>Neuron (Cambridge, Mass.), 2002-07, Vol.35 (1), p.51-63</ispartof><rights>2002 Cell Press</rights><rights>Copyright Elsevier Limited Jul 3, 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-cdab93d9fa16a127147ed72c054b2c8e7dd79cb9d87fac3fc3c70e39cee12d263</citedby><cites>FETCH-LOGICAL-c519t-cdab93d9fa16a127147ed72c054b2c8e7dd79cb9d87fac3fc3c70e39cee12d263</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0896-6273(02)00750-X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12123608$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Swiercz, Jakub M.</creatorcontrib><creatorcontrib>Kuner, Rohini</creatorcontrib><creatorcontrib>Behrens, Jürgen</creatorcontrib><creatorcontrib>Offermanns, Stefan</creatorcontrib><title>Plexin-B1 Directly Interacts with PDZ-RhoGEF/LARG to Regulate RhoA and Growth Cone Morphology</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>Plexins are widely expressed transmembrane proteins that, in the nervous system, mediate repulsive signals of semaphorins. However, the molecular nature of plexin-mediated signal transduction remains poorly understood. Here, we demonstrate that plexin-B family members associate through their C termini with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. Activation of plexin-B1 by semaphorin 4D regulates PDZ-RhoGEF/LARG activity leading to RhoA activation. In addition, a dominant-negative form of PDZ-RhoGEF blocks semaphorin 4D-induced growth cone collapse in primary hippocampal neurons. Our study indicates that the interaction of mammalian plexin-B family members with the multidomain proteins PDZ-RhoGEF and LARG represents an essential molecular link between plexin-B and localized, Rho-mediated downstream signaling events which underly various plexin-mediated cellular phenomena including axonal growth cone collapse.</description><subject>Animals</subject><subject>Antigens, CD</subject><subject>Cell Communication - genetics</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Membrane - metabolism</subject><subject>Cells, Cultured</subject><subject>Chick Embryo</subject><subject>Cytoskeleton</subject><subject>Digital cameras</subject><subject>Fetus</subject><subject>Growth Cones - metabolism</subject><subject>Growth Cones - ultrastructure</subject><subject>Guanine Nucleotide Exchange Factors - genetics</subject><subject>Guanine Nucleotide Exchange Factors - metabolism</subject><subject>Hippocampus - embryology</subject><subject>Hippocampus - growth & development</subject><subject>Hippocampus - metabolism</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Insects</subject><subject>Ligands</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mutation - genetics</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Protein Binding - genetics</subject><subject>Protein Structure, Tertiary - genetics</subject><subject>Proteins</subject><subject>Rats</subject><subject>Receptors, Cell Surface - genetics</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Regulation</subject><subject>Retinal Ganglion Cells - cytology</subject><subject>Retinal Ganglion Cells - metabolism</subject><subject>Rho Guanine Nucleotide Exchange Factors</subject><subject>rhoA GTP-Binding Protein - genetics</subject><subject>rhoA GTP-Binding Protein - metabolism</subject><subject>Semaphorins</subject><subject>Signal Transduction - genetics</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1rFDEUhoModlv9CUpAEL0Ym5PMJJOrsm7btbBiWRWKICGbnOlOmZ2syUzr_ntnP1DwpnAgcHjeNyQPIa-AfQAG8vQrK7XMJFfiHePvGVMFy26ekBEwrbIctH5KRn-RI3Kc0h1jkBcanpMj4MCFZOWI_Lxu8HfdZh-BntcRXdds6FXbYbSuS_Sh7pb0-vxHNl-G6cXl6Ww8n9Iu0Dne9o3tkA77MbWtp9MYHgZ2Elqkn0NcL0MTbjcvyLPKNglfHs4T8v3y4tvkUzb7Mr2ajGeZK0B3mfN2oYXXlQVpgSvIFXrFHSvyBXclKu-VdgvtS1VZJyonnGIotEME7rkUJ-Ttvncdw68eU2dWdXLYNLbF0CejQPNhxKMglLlUvOQD-OY_8C70sR0eYaBgQkmh5bau2FMuhpQiVmYd65WNGwPMbDWZnSazdWAYNztN5mbIvT6094sV-n-pg5cBONsDOPzafY3RJFdj69DvJBkf6keu-ANx26B8</recordid><startdate>20020703</startdate><enddate>20020703</enddate><creator>Swiercz, Jakub M.</creator><creator>Kuner, Rohini</creator><creator>Behrens, Jürgen</creator><creator>Offermanns, Stefan</creator><general>Elsevier Inc</general><general>Elsevier Limited</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20020703</creationdate><title>Plexin-B1 Directly Interacts with PDZ-RhoGEF/LARG to Regulate RhoA and Growth Cone Morphology</title><author>Swiercz, Jakub M. ; Kuner, Rohini ; Behrens, Jürgen ; Offermanns, Stefan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c519t-cdab93d9fa16a127147ed72c054b2c8e7dd79cb9d87fac3fc3c70e39cee12d263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Antigens, CD</topic><topic>Cell Communication - genetics</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Membrane - metabolism</topic><topic>Cells, Cultured</topic><topic>Chick Embryo</topic><topic>Cytoskeleton</topic><topic>Digital cameras</topic><topic>Fetus</topic><topic>Growth Cones - metabolism</topic><topic>Growth Cones - ultrastructure</topic><topic>Guanine Nucleotide Exchange Factors - genetics</topic><topic>Guanine Nucleotide Exchange Factors - metabolism</topic><topic>Hippocampus - embryology</topic><topic>Hippocampus - growth & development</topic><topic>Hippocampus - metabolism</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Insects</topic><topic>Ligands</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Mutation - genetics</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Protein Binding - genetics</topic><topic>Protein Structure, Tertiary - genetics</topic><topic>Proteins</topic><topic>Rats</topic><topic>Receptors, Cell Surface - genetics</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Regulation</topic><topic>Retinal Ganglion Cells - cytology</topic><topic>Retinal Ganglion Cells - metabolism</topic><topic>Rho Guanine Nucleotide Exchange Factors</topic><topic>rhoA GTP-Binding Protein - genetics</topic><topic>rhoA GTP-Binding Protein - metabolism</topic><topic>Semaphorins</topic><topic>Signal Transduction - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Swiercz, Jakub M.</creatorcontrib><creatorcontrib>Kuner, Rohini</creatorcontrib><creatorcontrib>Behrens, Jürgen</creatorcontrib><creatorcontrib>Offermanns, Stefan</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>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neuron (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Swiercz, Jakub M.</au><au>Kuner, Rohini</au><au>Behrens, Jürgen</au><au>Offermanns, Stefan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plexin-B1 Directly Interacts with PDZ-RhoGEF/LARG to Regulate RhoA and Growth Cone Morphology</atitle><jtitle>Neuron (Cambridge, Mass.)</jtitle><addtitle>Neuron</addtitle><date>2002-07-03</date><risdate>2002</risdate><volume>35</volume><issue>1</issue><spage>51</spage><epage>63</epage><pages>51-63</pages><issn>0896-6273</issn><eissn>1097-4199</eissn><abstract>Plexins are widely expressed transmembrane proteins that, in the nervous system, mediate repulsive signals of semaphorins. However, the molecular nature of plexin-mediated signal transduction remains poorly understood. Here, we demonstrate that plexin-B family members associate through their C termini with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. Activation of plexin-B1 by semaphorin 4D regulates PDZ-RhoGEF/LARG activity leading to RhoA activation. In addition, a dominant-negative form of PDZ-RhoGEF blocks semaphorin 4D-induced growth cone collapse in primary hippocampal neurons. Our study indicates that the interaction of mammalian plexin-B family members with the multidomain proteins PDZ-RhoGEF and LARG represents an essential molecular link between plexin-B and localized, Rho-mediated downstream signaling events which underly various plexin-mediated cellular phenomena including axonal growth cone collapse.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12123608</pmid><doi>10.1016/S0896-6273(02)00750-X</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0896-6273 |
| ispartof | Neuron (Cambridge, Mass.), 2002-07, Vol.35 (1), p.51-63 |
| issn | 0896-6273 1097-4199 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71921923 |
| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Antigens, CD Cell Communication - genetics Cell Differentiation - genetics Cell Membrane - metabolism Cells, Cultured Chick Embryo Cytoskeleton Digital cameras Fetus Growth Cones - metabolism Growth Cones - ultrastructure Guanine Nucleotide Exchange Factors - genetics Guanine Nucleotide Exchange Factors - metabolism Hippocampus - embryology Hippocampus - growth & development Hippocampus - metabolism Humans Immunohistochemistry Insects Ligands Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Mutation - genetics Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Protein Binding - genetics Protein Structure, Tertiary - genetics Proteins Rats Receptors, Cell Surface - genetics Receptors, Cell Surface - metabolism Regulation Retinal Ganglion Cells - cytology Retinal Ganglion Cells - metabolism Rho Guanine Nucleotide Exchange Factors rhoA GTP-Binding Protein - genetics rhoA GTP-Binding Protein - metabolism Semaphorins Signal Transduction - genetics |
| title | Plexin-B1 Directly Interacts with PDZ-RhoGEF/LARG to Regulate RhoA and Growth Cone Morphology |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T10%3A32%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Plexin-B1%20Directly%20Interacts%20with%20PDZ-RhoGEF/LARG%20to%20Regulate%20RhoA%20and%20Growth%20Cone%20Morphology&rft.jtitle=Neuron%20(Cambridge,%20Mass.)&rft.au=Swiercz,%20Jakub%20M.&rft.date=2002-07-03&rft.volume=35&rft.issue=1&rft.spage=51&rft.epage=63&rft.pages=51-63&rft.issn=0896-6273&rft.eissn=1097-4199&rft_id=info:doi/10.1016/S0896-6273(02)00750-X&rft_dat=%3Cproquest_cross%3E18467282%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1503763963&rft_id=info:pmid/12123608&rft_els_id=S089662730200750X&rfr_iscdi=true |