UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity
The receptor deleted in colorectal cancer (DCC) directs dynamic polarizing activities in animals toward its extracellular ligand netrin. How DCC polarizes toward netrin is poorly understood. By performing live-cell imaging of the DCC orthologue UNC-40 during anchor cell invasion in Caenorhabditis el...
Gespeichert in:
| Veröffentlicht in: | The Journal of cell biology 2014-09, Vol.206 (5), p.619-633 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 633 |
|---|---|
| container_issue | 5 |
| container_start_page | 619 |
| container_title | The Journal of cell biology |
| container_volume | 206 |
| creator | Wang, Zheng Linden, Lara M Naegeli, Kaleb M Ziel, Joshua W Chi, Qiuyi Hagedorn, Elliott J Savage, Natasha S Sherwood, David R |
| description | The receptor deleted in colorectal cancer (DCC) directs dynamic polarizing activities in animals toward its extracellular ligand netrin. How DCC polarizes toward netrin is poorly understood. By performing live-cell imaging of the DCC orthologue UNC-40 during anchor cell invasion in Caenorhabditis elegans, we have found that UNC-40 clusters, recruits F-actin effectors, and generates F-actin in the absence of UNC-6 (netrin). Time-lapse analyses revealed that UNC-40 clusters assemble, disassemble, and reform at periodic intervals in different regions of the cell membrane. This oscillatory behavior indicates that UNC-40 clusters through a mechanism involving interlinked positive (formation) and negative (disassembly) feedback. We show that endogenous UNC-6 and ectopically provided UNC-6 orient and stabilize UNC-40 clustering. Furthermore, the UNC-40-binding protein MADD-2 (a TRIM family protein) promotes ligand-independent clustering and robust UNC-40 polarization toward UNC-6. Together, our data suggest that UNC-6 (netrin) directs polarized responses by stabilizing UNC-40 clustering. We propose that ligand-independent UNC-40 clustering provides a robust and adaptable mechanism to polarize toward netrin. |
| doi_str_mv | 10.1083/jcb.201405026 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4151141</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3425700421</sourcerecordid><originalsourceid>FETCH-LOGICAL-c481t-dd49ac696a041f1a490e756f9b0563ab4adc9ea299bb1579bb2e20db069adf13</originalsourceid><addsrcrecordid>eNpd0c9v2yAUB3BUrVrTdMdeK6RdkoO7BwZsLpMqb_0hVeulOzOMcUrkmAzwpPSvH1HbqNsFhPjw9B5fhM4JXBKoyy9r015SIAw4UHGEZoQzKOp8_oBmAJQUklN-gk5jXAMAq1j5EZ1Qnlkp6xn69fNHUwi8GG0KblzimHTrBvdsI_bRuGHQyYcdNsMUk81ihX2P05PF-3cM8OJb0yxxsMZuM8TJYx-cHRPe-kEHl3Zn6LjXQ7SfXvc5erz-_tjcFvcPN3fN1X1hWE1S0XVMaiOk0MBITzSTYCsuetkCF6Vume6MtJpK2baEV3mllkLXgpC660k5R19fym6ndmM7k1sIelDb4DY67JTXTv17M7ontfJ_FCOcELYvsHgtEPzvycakNi4amz9gtH6KinAuBc2UZ_r5P7r2UxjzdFkJEFVVU5lV8aJM8DEG2x-aIaD20akcnTpEl_3F-wkO-i2r8i8mDpQI</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1560677829</pqid></control><display><type>article</type><title>UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Wang, Zheng ; Linden, Lara M ; Naegeli, Kaleb M ; Ziel, Joshua W ; Chi, Qiuyi ; Hagedorn, Elliott J ; Savage, Natasha S ; Sherwood, David R</creator><creatorcontrib>Wang, Zheng ; Linden, Lara M ; Naegeli, Kaleb M ; Ziel, Joshua W ; Chi, Qiuyi ; Hagedorn, Elliott J ; Savage, Natasha S ; Sherwood, David R</creatorcontrib><description>The receptor deleted in colorectal cancer (DCC) directs dynamic polarizing activities in animals toward its extracellular ligand netrin. How DCC polarizes toward netrin is poorly understood. By performing live-cell imaging of the DCC orthologue UNC-40 during anchor cell invasion in Caenorhabditis elegans, we have found that UNC-40 clusters, recruits F-actin effectors, and generates F-actin in the absence of UNC-6 (netrin). Time-lapse analyses revealed that UNC-40 clusters assemble, disassemble, and reform at periodic intervals in different regions of the cell membrane. This oscillatory behavior indicates that UNC-40 clusters through a mechanism involving interlinked positive (formation) and negative (disassembly) feedback. We show that endogenous UNC-6 and ectopically provided UNC-6 orient and stabilize UNC-40 clustering. Furthermore, the UNC-40-binding protein MADD-2 (a TRIM family protein) promotes ligand-independent clustering and robust UNC-40 polarization toward UNC-6. Together, our data suggest that UNC-6 (netrin) directs polarized responses by stabilizing UNC-40 clustering. We propose that ligand-independent UNC-40 clustering provides a robust and adaptable mechanism to polarize toward netrin.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.201405026</identifier><identifier>PMID: 25154398</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Actins - metabolism ; Animals ; Caenorhabditis elegans - cytology ; Caenorhabditis elegans - metabolism ; Caenorhabditis elegans Proteins - metabolism ; Caenorhabditis elegans Proteins - physiology ; Cell Adhesion Molecules - metabolism ; Cell Polarity ; Cellular biology ; Colorectal cancer ; Female ; Intracellular Signaling Peptides and Proteins - metabolism ; Ligands ; Nematodes ; Nerve Tissue Proteins - physiology ; Netrins ; Protein Multimerization ; Protein Stability ; Protein Transport ; Proteins ; Scientific imaging ; Uterus - cytology</subject><ispartof>The Journal of cell biology, 2014-09, Vol.206 (5), p.619-633</ispartof><rights>2014 Wang et al.</rights><rights>Copyright Rockefeller University Press Sep 1, 2014</rights><rights>2014 Wang et al. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-dd49ac696a041f1a490e756f9b0563ab4adc9ea299bb1579bb2e20db069adf13</citedby><cites>FETCH-LOGICAL-c481t-dd49ac696a041f1a490e756f9b0563ab4adc9ea299bb1579bb2e20db069adf13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25154398$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Zheng</creatorcontrib><creatorcontrib>Linden, Lara M</creatorcontrib><creatorcontrib>Naegeli, Kaleb M</creatorcontrib><creatorcontrib>Ziel, Joshua W</creatorcontrib><creatorcontrib>Chi, Qiuyi</creatorcontrib><creatorcontrib>Hagedorn, Elliott J</creatorcontrib><creatorcontrib>Savage, Natasha S</creatorcontrib><creatorcontrib>Sherwood, David R</creatorcontrib><title>UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>The receptor deleted in colorectal cancer (DCC) directs dynamic polarizing activities in animals toward its extracellular ligand netrin. How DCC polarizes toward netrin is poorly understood. By performing live-cell imaging of the DCC orthologue UNC-40 during anchor cell invasion in Caenorhabditis elegans, we have found that UNC-40 clusters, recruits F-actin effectors, and generates F-actin in the absence of UNC-6 (netrin). Time-lapse analyses revealed that UNC-40 clusters assemble, disassemble, and reform at periodic intervals in different regions of the cell membrane. This oscillatory behavior indicates that UNC-40 clusters through a mechanism involving interlinked positive (formation) and negative (disassembly) feedback. We show that endogenous UNC-6 and ectopically provided UNC-6 orient and stabilize UNC-40 clustering. Furthermore, the UNC-40-binding protein MADD-2 (a TRIM family protein) promotes ligand-independent clustering and robust UNC-40 polarization toward UNC-6. Together, our data suggest that UNC-6 (netrin) directs polarized responses by stabilizing UNC-40 clustering. We propose that ligand-independent UNC-40 clustering provides a robust and adaptable mechanism to polarize toward netrin.</description><subject>Actins - metabolism</subject><subject>Animals</subject><subject>Caenorhabditis elegans - cytology</subject><subject>Caenorhabditis elegans - metabolism</subject><subject>Caenorhabditis elegans Proteins - metabolism</subject><subject>Caenorhabditis elegans Proteins - physiology</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cell Polarity</subject><subject>Cellular biology</subject><subject>Colorectal cancer</subject><subject>Female</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Ligands</subject><subject>Nematodes</subject><subject>Nerve Tissue Proteins - physiology</subject><subject>Netrins</subject><subject>Protein Multimerization</subject><subject>Protein Stability</subject><subject>Protein Transport</subject><subject>Proteins</subject><subject>Scientific imaging</subject><subject>Uterus - cytology</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0c9v2yAUB3BUrVrTdMdeK6RdkoO7BwZsLpMqb_0hVeulOzOMcUrkmAzwpPSvH1HbqNsFhPjw9B5fhM4JXBKoyy9r015SIAw4UHGEZoQzKOp8_oBmAJQUklN-gk5jXAMAq1j5EZ1Qnlkp6xn69fNHUwi8GG0KblzimHTrBvdsI_bRuGHQyYcdNsMUk81ihX2P05PF-3cM8OJb0yxxsMZuM8TJYx-cHRPe-kEHl3Zn6LjXQ7SfXvc5erz-_tjcFvcPN3fN1X1hWE1S0XVMaiOk0MBITzSTYCsuetkCF6Vume6MtJpK2baEV3mllkLXgpC660k5R19fym6ndmM7k1sIelDb4DY67JTXTv17M7ontfJ_FCOcELYvsHgtEPzvycakNi4amz9gtH6KinAuBc2UZ_r5P7r2UxjzdFkJEFVVU5lV8aJM8DEG2x-aIaD20akcnTpEl_3F-wkO-i2r8i8mDpQI</recordid><startdate>20140901</startdate><enddate>20140901</enddate><creator>Wang, Zheng</creator><creator>Linden, Lara M</creator><creator>Naegeli, Kaleb M</creator><creator>Ziel, Joshua W</creator><creator>Chi, Qiuyi</creator><creator>Hagedorn, Elliott J</creator><creator>Savage, Natasha S</creator><creator>Sherwood, David R</creator><general>Rockefeller University Press</general><general>The 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></search><sort><creationdate>20140901</creationdate><title>UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity</title><author>Wang, Zheng ; Linden, Lara M ; Naegeli, Kaleb M ; Ziel, Joshua W ; Chi, Qiuyi ; Hagedorn, Elliott J ; Savage, Natasha S ; Sherwood, David R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-dd49ac696a041f1a490e756f9b0563ab4adc9ea299bb1579bb2e20db069adf13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Actins - metabolism</topic><topic>Animals</topic><topic>Caenorhabditis elegans - cytology</topic><topic>Caenorhabditis elegans - metabolism</topic><topic>Caenorhabditis elegans Proteins - metabolism</topic><topic>Caenorhabditis elegans Proteins - physiology</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Cell Polarity</topic><topic>Cellular biology</topic><topic>Colorectal cancer</topic><topic>Female</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Ligands</topic><topic>Nematodes</topic><topic>Nerve Tissue Proteins - physiology</topic><topic>Netrins</topic><topic>Protein Multimerization</topic><topic>Protein Stability</topic><topic>Protein Transport</topic><topic>Proteins</topic><topic>Scientific imaging</topic><topic>Uterus - cytology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Zheng</creatorcontrib><creatorcontrib>Linden, Lara M</creatorcontrib><creatorcontrib>Naegeli, Kaleb M</creatorcontrib><creatorcontrib>Ziel, Joshua W</creatorcontrib><creatorcontrib>Chi, Qiuyi</creatorcontrib><creatorcontrib>Hagedorn, Elliott J</creatorcontrib><creatorcontrib>Savage, Natasha S</creatorcontrib><creatorcontrib>Sherwood, David R</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>Wang, Zheng</au><au>Linden, Lara M</au><au>Naegeli, Kaleb M</au><au>Ziel, Joshua W</au><au>Chi, Qiuyi</au><au>Hagedorn, Elliott J</au><au>Savage, Natasha S</au><au>Sherwood, David R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>2014-09-01</date><risdate>2014</risdate><volume>206</volume><issue>5</issue><spage>619</spage><epage>633</epage><pages>619-633</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><coden>JCLBA3</coden><abstract>The receptor deleted in colorectal cancer (DCC) directs dynamic polarizing activities in animals toward its extracellular ligand netrin. How DCC polarizes toward netrin is poorly understood. By performing live-cell imaging of the DCC orthologue UNC-40 during anchor cell invasion in Caenorhabditis elegans, we have found that UNC-40 clusters, recruits F-actin effectors, and generates F-actin in the absence of UNC-6 (netrin). Time-lapse analyses revealed that UNC-40 clusters assemble, disassemble, and reform at periodic intervals in different regions of the cell membrane. This oscillatory behavior indicates that UNC-40 clusters through a mechanism involving interlinked positive (formation) and negative (disassembly) feedback. We show that endogenous UNC-6 and ectopically provided UNC-6 orient and stabilize UNC-40 clustering. Furthermore, the UNC-40-binding protein MADD-2 (a TRIM family protein) promotes ligand-independent clustering and robust UNC-40 polarization toward UNC-6. Together, our data suggest that UNC-6 (netrin) directs polarized responses by stabilizing UNC-40 clustering. We propose that ligand-independent UNC-40 clustering provides a robust and adaptable mechanism to polarize toward netrin.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>25154398</pmid><doi>10.1083/jcb.201405026</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9525 |
| ispartof | The Journal of cell biology, 2014-09, Vol.206 (5), p.619-633 |
| issn | 0021-9525 1540-8140 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4151141 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Actins - metabolism Animals Caenorhabditis elegans - cytology Caenorhabditis elegans - metabolism Caenorhabditis elegans Proteins - metabolism Caenorhabditis elegans Proteins - physiology Cell Adhesion Molecules - metabolism Cell Polarity Cellular biology Colorectal cancer Female Intracellular Signaling Peptides and Proteins - metabolism Ligands Nematodes Nerve Tissue Proteins - physiology Netrins Protein Multimerization Protein Stability Protein Transport Proteins Scientific imaging Uterus - cytology |
| title | UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T11%3A37%3A09IST&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=UNC-6%20(netrin)%20stabilizes%20oscillatory%20clustering%20of%20the%20UNC-40%20(DCC)%20receptor%20to%20orient%20polarity&rft.jtitle=The%20Journal%20of%20cell%20biology&rft.au=Wang,%20Zheng&rft.date=2014-09-01&rft.volume=206&rft.issue=5&rft.spage=619&rft.epage=633&rft.pages=619-633&rft.issn=0021-9525&rft.eissn=1540-8140&rft.coden=JCLBA3&rft_id=info:doi/10.1083/jcb.201405026&rft_dat=%3Cproquest_pubme%3E3425700421%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=1560677829&rft_id=info:pmid/25154398&rfr_iscdi=true |