Cthrc1 Selectively Activates the Planar Cell Polarity Pathway of Wnt Signaling by Stabilizing the Wnt-Receptor Complex
Vertebrate Wnt proteins activate several distinct pathways. Intrinsic differences among Wnt ligands and Frizzled (Fzd) receptors, and the availability of pathway-specific coreceptors, LRP5/6, and Ror2, affect pathway selection. Here, we show that a secreted glycoprotein, Cthrc1, is involved in selec...
Gespeichert in:
| Veröffentlicht in: | Developmental cell 2008-07, Vol.15 (1), p.23-36 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 36 |
|---|---|
| container_issue | 1 |
| container_start_page | 23 |
| container_title | Developmental cell |
| container_volume | 15 |
| creator | Yamamoto, Shinji Nishimura, Osamu Misaki, Kazuyo Nishita, Michiru Minami, Yasuhiro Yonemura, Shigenobu Tarui, Hiroshi Sasaki, Hiroshi |
| description | Vertebrate Wnt proteins activate several distinct pathways. Intrinsic differences among Wnt ligands and Frizzled (Fzd) receptors, and the availability of pathway-specific coreceptors, LRP5/6, and Ror2, affect pathway selection. Here, we show that a secreted glycoprotein, Cthrc1, is involved in selective activation of the planar cell polarity (PCP) pathway by Wnt proteins. Although
Cthrc1 null mutant mice appeared normal, the introduction of a heterozygous mutation of a PCP gene,
Vangl2, resulted in abnormalities characteristic of PCP mutants. In HEK293T cells, Cthrc1 activated the PCP pathway but suppressed the canonical pathway. Cell-surface-anchored Cthrc1 bound to Wnt proteins, Fzd proteins, and Ror2 and enhanced the interaction of Wnt proteins and Fzd/Ror2 by forming the Cthrc1-Wnt-Fzd/Ror2 complex. Consistent with this, Ror2 mutant mice also showed PCP-related abnormalities in the inner ear. These results suggest that Cthrc1 is a Wnt cofactor protein that selectively activates the Wnt/PCP pathway by stabilizing ligand-receptor interaction. |
| doi_str_mv | 10.1016/j.devcel.2008.05.007 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69301637</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1534580708002074</els_id><sourcerecordid>69301637</sourcerecordid><originalsourceid>FETCH-LOGICAL-c502t-304c90879c6675482f9a38ccabb4251ad5b54d7e236d5f98dbcfca34d15eaaa23</originalsourceid><addsrcrecordid>eNp9kV2L1DAUhoMo7rr6D0Ryo3etSdO06Y2wDOsHLDg4ipfhNDndyZBpxyQzWn-9KTPonVc5ged9yXlCyEvOSs5483ZXWjwZ9GXFmCqZLBlrH5FrrlpVcCn54zxLURdSsfaKPItxx3KMK_aUXHHVsIYLdU1Oq7QNhtMNejTJndDP9HYZIGGkaYt07WGEQFfoPV1PHoJLM11D2v6EmU4D_T4munEPI3g3PtB-ppsEvfPu93JdCjJQfEGDhzTlmml_8PjrOXkygI_44nLekG_v776uPhb3nz98Wt3eF0ayKhWC1aZjqu1M07SyVtXQgVDGQN_XleRgZS9r22IlGiuHTtneDAZEbblEAKjEDXlz7j2E6ccRY9J7F7O0vBNOx6ibTmQpos1gfQZNmGIMOOhDcHsIs-ZML771Tp9968W3ZlJn3zn26tJ_7Pdo_4UugjPw-gJANOCHAKNx8S9XMcmUapeid2cOs42Tw6CjcTgatC7kj9F2cv9_yR8Q46Fq</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>69301637</pqid></control><display><type>article</type><title>Cthrc1 Selectively Activates the Planar Cell Polarity Pathway of Wnt Signaling by Stabilizing the Wnt-Receptor Complex</title><source>MEDLINE</source><source>Cell Press Free Archives</source><source>ScienceDirect Journals (5 years ago - present)</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Yamamoto, Shinji ; Nishimura, Osamu ; Misaki, Kazuyo ; Nishita, Michiru ; Minami, Yasuhiro ; Yonemura, Shigenobu ; Tarui, Hiroshi ; Sasaki, Hiroshi</creator><creatorcontrib>Yamamoto, Shinji ; Nishimura, Osamu ; Misaki, Kazuyo ; Nishita, Michiru ; Minami, Yasuhiro ; Yonemura, Shigenobu ; Tarui, Hiroshi ; Sasaki, Hiroshi</creatorcontrib><description>Vertebrate Wnt proteins activate several distinct pathways. Intrinsic differences among Wnt ligands and Frizzled (Fzd) receptors, and the availability of pathway-specific coreceptors, LRP5/6, and Ror2, affect pathway selection. Here, we show that a secreted glycoprotein, Cthrc1, is involved in selective activation of the planar cell polarity (PCP) pathway by Wnt proteins. Although
Cthrc1 null mutant mice appeared normal, the introduction of a heterozygous mutation of a PCP gene,
Vangl2, resulted in abnormalities characteristic of PCP mutants. In HEK293T cells, Cthrc1 activated the PCP pathway but suppressed the canonical pathway. Cell-surface-anchored Cthrc1 bound to Wnt proteins, Fzd proteins, and Ror2 and enhanced the interaction of Wnt proteins and Fzd/Ror2 by forming the Cthrc1-Wnt-Fzd/Ror2 complex. Consistent with this, Ror2 mutant mice also showed PCP-related abnormalities in the inner ear. These results suggest that Cthrc1 is a Wnt cofactor protein that selectively activates the Wnt/PCP pathway by stabilizing ligand-receptor interaction.</description><identifier>ISSN: 1534-5807</identifier><identifier>EISSN: 1878-1551</identifier><identifier>DOI: 10.1016/j.devcel.2008.05.007</identifier><identifier>PMID: 18606138</identifier><language>eng</language><publisher>Cambridge, MA: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Cell differentiation, maturation, development, hematopoiesis ; Cell Line ; Cell physiology ; Cell Polarity ; Cell receptors ; Cell structures and functions ; DEVBIO ; Embryo, Mammalian ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Extracellular Matrix Proteins - genetics ; Extracellular Matrix Proteins - metabolism ; Frizzled Receptors - genetics ; Frizzled Receptors - metabolism ; Fundamental and applied biological sciences. Psychology ; Glycoproteins - genetics ; Glycoproteins - metabolism ; Hair Cells, Auditory, Inner - cytology ; Humans ; Kidney - cytology ; Lac Operon - genetics ; Ligands ; Mice ; Mice, Knockout ; Miscellaneous ; Molecular and cellular biology ; Mutation ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Receptor Protein-Tyrosine Kinases - genetics ; Receptor Protein-Tyrosine Kinases - metabolism ; Receptor Tyrosine Kinase-like Orphan Receptors ; Recombination, Genetic ; Signal Transduction ; SIGNALING ; Tissue Distribution ; Wnt Proteins - genetics ; Wnt Proteins - metabolism</subject><ispartof>Developmental cell, 2008-07, Vol.15 (1), p.23-36</ispartof><rights>2008 Elsevier Inc.</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c502t-304c90879c6675482f9a38ccabb4251ad5b54d7e236d5f98dbcfca34d15eaaa23</citedby><cites>FETCH-LOGICAL-c502t-304c90879c6675482f9a38ccabb4251ad5b54d7e236d5f98dbcfca34d15eaaa23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.devcel.2008.05.007$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20508877$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18606138$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamamoto, Shinji</creatorcontrib><creatorcontrib>Nishimura, Osamu</creatorcontrib><creatorcontrib>Misaki, Kazuyo</creatorcontrib><creatorcontrib>Nishita, Michiru</creatorcontrib><creatorcontrib>Minami, Yasuhiro</creatorcontrib><creatorcontrib>Yonemura, Shigenobu</creatorcontrib><creatorcontrib>Tarui, Hiroshi</creatorcontrib><creatorcontrib>Sasaki, Hiroshi</creatorcontrib><title>Cthrc1 Selectively Activates the Planar Cell Polarity Pathway of Wnt Signaling by Stabilizing the Wnt-Receptor Complex</title><title>Developmental cell</title><addtitle>Dev Cell</addtitle><description>Vertebrate Wnt proteins activate several distinct pathways. Intrinsic differences among Wnt ligands and Frizzled (Fzd) receptors, and the availability of pathway-specific coreceptors, LRP5/6, and Ror2, affect pathway selection. Here, we show that a secreted glycoprotein, Cthrc1, is involved in selective activation of the planar cell polarity (PCP) pathway by Wnt proteins. Although
Cthrc1 null mutant mice appeared normal, the introduction of a heterozygous mutation of a PCP gene,
Vangl2, resulted in abnormalities characteristic of PCP mutants. In HEK293T cells, Cthrc1 activated the PCP pathway but suppressed the canonical pathway. Cell-surface-anchored Cthrc1 bound to Wnt proteins, Fzd proteins, and Ror2 and enhanced the interaction of Wnt proteins and Fzd/Ror2 by forming the Cthrc1-Wnt-Fzd/Ror2 complex. Consistent with this, Ror2 mutant mice also showed PCP-related abnormalities in the inner ear. These results suggest that Cthrc1 is a Wnt cofactor protein that selectively activates the Wnt/PCP pathway by stabilizing ligand-receptor interaction.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell Line</subject><subject>Cell physiology</subject><subject>Cell Polarity</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>DEVBIO</subject><subject>Embryo, Mammalian</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Extracellular Matrix Proteins - genetics</subject><subject>Extracellular Matrix Proteins - metabolism</subject><subject>Frizzled Receptors - genetics</subject><subject>Frizzled Receptors - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glycoproteins - genetics</subject><subject>Glycoproteins - metabolism</subject><subject>Hair Cells, Auditory, Inner - cytology</subject><subject>Humans</subject><subject>Kidney - cytology</subject><subject>Lac Operon - genetics</subject><subject>Ligands</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Miscellaneous</subject><subject>Molecular and cellular biology</subject><subject>Mutation</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Receptor Protein-Tyrosine Kinases - genetics</subject><subject>Receptor Protein-Tyrosine Kinases - metabolism</subject><subject>Receptor Tyrosine Kinase-like Orphan Receptors</subject><subject>Recombination, Genetic</subject><subject>Signal Transduction</subject><subject>SIGNALING</subject><subject>Tissue Distribution</subject><subject>Wnt Proteins - genetics</subject><subject>Wnt Proteins - metabolism</subject><issn>1534-5807</issn><issn>1878-1551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV2L1DAUhoMo7rr6D0Ryo3etSdO06Y2wDOsHLDg4ipfhNDndyZBpxyQzWn-9KTPonVc5ged9yXlCyEvOSs5483ZXWjwZ9GXFmCqZLBlrH5FrrlpVcCn54zxLURdSsfaKPItxx3KMK_aUXHHVsIYLdU1Oq7QNhtMNejTJndDP9HYZIGGkaYt07WGEQFfoPV1PHoJLM11D2v6EmU4D_T4munEPI3g3PtB-ppsEvfPu93JdCjJQfEGDhzTlmml_8PjrOXkygI_44nLekG_v776uPhb3nz98Wt3eF0ayKhWC1aZjqu1M07SyVtXQgVDGQN_XleRgZS9r22IlGiuHTtneDAZEbblEAKjEDXlz7j2E6ccRY9J7F7O0vBNOx6ibTmQpos1gfQZNmGIMOOhDcHsIs-ZML771Tp9968W3ZlJn3zn26tJ_7Pdo_4UugjPw-gJANOCHAKNx8S9XMcmUapeid2cOs42Tw6CjcTgatC7kj9F2cv9_yR8Q46Fq</recordid><startdate>20080701</startdate><enddate>20080701</enddate><creator>Yamamoto, Shinji</creator><creator>Nishimura, Osamu</creator><creator>Misaki, Kazuyo</creator><creator>Nishita, Michiru</creator><creator>Minami, Yasuhiro</creator><creator>Yonemura, Shigenobu</creator><creator>Tarui, Hiroshi</creator><creator>Sasaki, Hiroshi</creator><general>Elsevier Inc</general><general>Cell Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</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>7X8</scope></search><sort><creationdate>20080701</creationdate><title>Cthrc1 Selectively Activates the Planar Cell Polarity Pathway of Wnt Signaling by Stabilizing the Wnt-Receptor Complex</title><author>Yamamoto, Shinji ; Nishimura, Osamu ; Misaki, Kazuyo ; Nishita, Michiru ; Minami, Yasuhiro ; Yonemura, Shigenobu ; Tarui, Hiroshi ; Sasaki, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c502t-304c90879c6675482f9a38ccabb4251ad5b54d7e236d5f98dbcfca34d15eaaa23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell Line</topic><topic>Cell physiology</topic><topic>Cell Polarity</topic><topic>Cell receptors</topic><topic>Cell structures and functions</topic><topic>DEVBIO</topic><topic>Embryo, Mammalian</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Extracellular Matrix Proteins - genetics</topic><topic>Extracellular Matrix Proteins - metabolism</topic><topic>Frizzled Receptors - genetics</topic><topic>Frizzled Receptors - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glycoproteins - genetics</topic><topic>Glycoproteins - metabolism</topic><topic>Hair Cells, Auditory, Inner - cytology</topic><topic>Humans</topic><topic>Kidney - cytology</topic><topic>Lac Operon - genetics</topic><topic>Ligands</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Miscellaneous</topic><topic>Molecular and cellular biology</topic><topic>Mutation</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Receptor Protein-Tyrosine Kinases - genetics</topic><topic>Receptor Protein-Tyrosine Kinases - metabolism</topic><topic>Receptor Tyrosine Kinase-like Orphan Receptors</topic><topic>Recombination, Genetic</topic><topic>Signal Transduction</topic><topic>SIGNALING</topic><topic>Tissue Distribution</topic><topic>Wnt Proteins - genetics</topic><topic>Wnt Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamamoto, Shinji</creatorcontrib><creatorcontrib>Nishimura, Osamu</creatorcontrib><creatorcontrib>Misaki, Kazuyo</creatorcontrib><creatorcontrib>Nishita, Michiru</creatorcontrib><creatorcontrib>Minami, Yasuhiro</creatorcontrib><creatorcontrib>Yonemura, Shigenobu</creatorcontrib><creatorcontrib>Tarui, Hiroshi</creatorcontrib><creatorcontrib>Sasaki, Hiroshi</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><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>Developmental cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamamoto, Shinji</au><au>Nishimura, Osamu</au><au>Misaki, Kazuyo</au><au>Nishita, Michiru</au><au>Minami, Yasuhiro</au><au>Yonemura, Shigenobu</au><au>Tarui, Hiroshi</au><au>Sasaki, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cthrc1 Selectively Activates the Planar Cell Polarity Pathway of Wnt Signaling by Stabilizing the Wnt-Receptor Complex</atitle><jtitle>Developmental cell</jtitle><addtitle>Dev Cell</addtitle><date>2008-07-01</date><risdate>2008</risdate><volume>15</volume><issue>1</issue><spage>23</spage><epage>36</epage><pages>23-36</pages><issn>1534-5807</issn><eissn>1878-1551</eissn><abstract>Vertebrate Wnt proteins activate several distinct pathways. Intrinsic differences among Wnt ligands and Frizzled (Fzd) receptors, and the availability of pathway-specific coreceptors, LRP5/6, and Ror2, affect pathway selection. Here, we show that a secreted glycoprotein, Cthrc1, is involved in selective activation of the planar cell polarity (PCP) pathway by Wnt proteins. Although
Cthrc1 null mutant mice appeared normal, the introduction of a heterozygous mutation of a PCP gene,
Vangl2, resulted in abnormalities characteristic of PCP mutants. In HEK293T cells, Cthrc1 activated the PCP pathway but suppressed the canonical pathway. Cell-surface-anchored Cthrc1 bound to Wnt proteins, Fzd proteins, and Ror2 and enhanced the interaction of Wnt proteins and Fzd/Ror2 by forming the Cthrc1-Wnt-Fzd/Ror2 complex. Consistent with this, Ror2 mutant mice also showed PCP-related abnormalities in the inner ear. These results suggest that Cthrc1 is a Wnt cofactor protein that selectively activates the Wnt/PCP pathway by stabilizing ligand-receptor interaction.</abstract><cop>Cambridge, MA</cop><pub>Elsevier Inc</pub><pmid>18606138</pmid><doi>10.1016/j.devcel.2008.05.007</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1534-5807 |
| ispartof | Developmental cell, 2008-07, Vol.15 (1), p.23-36 |
| issn | 1534-5807 1878-1551 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69301637 |
| source | MEDLINE; Cell Press Free Archives; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Biological and medical sciences Cell differentiation, maturation, development, hematopoiesis Cell Line Cell physiology Cell Polarity Cell receptors Cell structures and functions DEVBIO Embryo, Mammalian Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Extracellular Matrix Proteins - genetics Extracellular Matrix Proteins - metabolism Frizzled Receptors - genetics Frizzled Receptors - metabolism Fundamental and applied biological sciences. Psychology Glycoproteins - genetics Glycoproteins - metabolism Hair Cells, Auditory, Inner - cytology Humans Kidney - cytology Lac Operon - genetics Ligands Mice Mice, Knockout Miscellaneous Molecular and cellular biology Mutation Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Receptor Protein-Tyrosine Kinases - genetics Receptor Protein-Tyrosine Kinases - metabolism Receptor Tyrosine Kinase-like Orphan Receptors Recombination, Genetic Signal Transduction SIGNALING Tissue Distribution Wnt Proteins - genetics Wnt Proteins - metabolism |
| title | Cthrc1 Selectively Activates the Planar Cell Polarity Pathway of Wnt Signaling by Stabilizing the Wnt-Receptor Complex |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T08%3A58%3A36IST&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=Cthrc1%20Selectively%20Activates%20the%20Planar%20Cell%20Polarity%20Pathway%20of%20Wnt%20Signaling%20by%20Stabilizing%20the%20Wnt-Receptor%20Complex&rft.jtitle=Developmental%20cell&rft.au=Yamamoto,%20Shinji&rft.date=2008-07-01&rft.volume=15&rft.issue=1&rft.spage=23&rft.epage=36&rft.pages=23-36&rft.issn=1534-5807&rft.eissn=1878-1551&rft_id=info:doi/10.1016/j.devcel.2008.05.007&rft_dat=%3Cproquest_cross%3E69301637%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=69301637&rft_id=info:pmid/18606138&rft_els_id=S1534580708002074&rfr_iscdi=true |