Daam2 couples translocation and clustering of Wnt receptor signalosomes through Rac1
Wnt signaling plays a critical role in development across species and is dysregulated in a host of human diseases. A key step in signal transduction is the formation of Wnt receptor signalosomes, during which a large number of components translocate to the membrane, cluster together and amplify down...
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| Veröffentlicht in: | Journal of cell science 2021-01, Vol.134 (2) |
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| container_title | Journal of cell science |
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| creator | Cristobal, Carlo D Ye, Qi Jo, Juyeon Ding, Xiaoyun Wang, Chih-Yen Cortes, Diego Chen, Zheng Lee, Hyun Kyoung |
| description | Wnt signaling plays a critical role in development across species and is dysregulated in a host of human diseases. A key step in signal transduction is the formation of Wnt receptor signalosomes, during which a large number of components translocate to the membrane, cluster together and amplify downstream signaling. However, the molecular processes that coordinate these events remain poorly defined. Here, we show that Daam2 regulates canonical Wnt signaling via the PIP
-PIP5K axis through its association with Rac1. Clustering of Daam2-mediated Wnt receptor complexes requires both Rac1 and PIP5K, and PIP5K promotes membrane localization of these complexes in a Rac1-dependent manner. Importantly, the localization of Daam2 complexes and Daam2-mediated canonical Wnt signaling is dependent upon actin polymerization. These studies - in chick spinal cord and human and monkey cell lines - highlight novel roles for Rac1 and the actin cytoskeleton in the regulation of canonical Wnt signaling and define Daam2 as a key scaffolding hub that coordinates membrane translocation and signalosome clustering. |
| doi_str_mv | 10.1242/jcs.251140 |
| format | Article |
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-PIP5K axis through its association with Rac1. Clustering of Daam2-mediated Wnt receptor complexes requires both Rac1 and PIP5K, and PIP5K promotes membrane localization of these complexes in a Rac1-dependent manner. Importantly, the localization of Daam2 complexes and Daam2-mediated canonical Wnt signaling is dependent upon actin polymerization. These studies - in chick spinal cord and human and monkey cell lines - highlight novel roles for Rac1 and the actin cytoskeleton in the regulation of canonical Wnt signaling and define Daam2 as a key scaffolding hub that coordinates membrane translocation and signalosome clustering.</description><identifier>ISSN: 0021-9533</identifier><identifier>EISSN: 1477-9137</identifier><identifier>DOI: 10.1242/jcs.251140</identifier><identifier>PMID: 33310913</identifier><language>eng</language><publisher>England: The Company of Biologists Ltd</publisher><subject>Animals ; Carrier Proteins ; Cell Line ; Chickens ; Cluster Analysis ; Haplorhini ; Humans ; Mice ; Microfilament Proteins ; Phosphorylation ; rac1 GTP-Binding Protein - genetics ; rac1 GTP-Binding Protein - metabolism ; rho GTP-Binding Proteins ; Spinal Cord - metabolism ; Wnt Signaling Pathway</subject><ispartof>Journal of cell science, 2021-01, Vol.134 (2)</ispartof><rights>2021. Published by The Company of Biologists Ltd.</rights><rights>2021. Published by The Company of Biologists Ltd 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-cd0ce2e1334d60a6f0532dfbb6b0165dd28215e7680ac308812c3426768847e3</citedby><cites>FETCH-LOGICAL-c378t-cd0ce2e1334d60a6f0532dfbb6b0165dd28215e7680ac308812c3426768847e3</cites><orcidid>0000-0001-5793-4398</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3664,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33310913$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cristobal, Carlo D</creatorcontrib><creatorcontrib>Ye, Qi</creatorcontrib><creatorcontrib>Jo, Juyeon</creatorcontrib><creatorcontrib>Ding, Xiaoyun</creatorcontrib><creatorcontrib>Wang, Chih-Yen</creatorcontrib><creatorcontrib>Cortes, Diego</creatorcontrib><creatorcontrib>Chen, Zheng</creatorcontrib><creatorcontrib>Lee, Hyun Kyoung</creatorcontrib><title>Daam2 couples translocation and clustering of Wnt receptor signalosomes through Rac1</title><title>Journal of cell science</title><addtitle>J Cell Sci</addtitle><description>Wnt signaling plays a critical role in development across species and is dysregulated in a host of human diseases. A key step in signal transduction is the formation of Wnt receptor signalosomes, during which a large number of components translocate to the membrane, cluster together and amplify downstream signaling. However, the molecular processes that coordinate these events remain poorly defined. Here, we show that Daam2 regulates canonical Wnt signaling via the PIP
-PIP5K axis through its association with Rac1. Clustering of Daam2-mediated Wnt receptor complexes requires both Rac1 and PIP5K, and PIP5K promotes membrane localization of these complexes in a Rac1-dependent manner. Importantly, the localization of Daam2 complexes and Daam2-mediated canonical Wnt signaling is dependent upon actin polymerization. These studies - in chick spinal cord and human and monkey cell lines - highlight novel roles for Rac1 and the actin cytoskeleton in the regulation of canonical Wnt signaling and define Daam2 as a key scaffolding hub that coordinates membrane translocation and signalosome clustering.</description><subject>Animals</subject><subject>Carrier Proteins</subject><subject>Cell Line</subject><subject>Chickens</subject><subject>Cluster Analysis</subject><subject>Haplorhini</subject><subject>Humans</subject><subject>Mice</subject><subject>Microfilament Proteins</subject><subject>Phosphorylation</subject><subject>rac1 GTP-Binding Protein - genetics</subject><subject>rac1 GTP-Binding Protein - metabolism</subject><subject>rho GTP-Binding Proteins</subject><subject>Spinal Cord - metabolism</subject><subject>Wnt Signaling Pathway</subject><issn>0021-9533</issn><issn>1477-9137</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkV1LwzAUhoMobk5v_AGSSxE689Em6Y0g8xMGggy8DGmadh1tUpNW8N-bsTn06sA5z3nPy3kBuMRojklKbjc6zEmGcYqOwBSnnCc5pvwYTBEiOMkzSifgLIQNQoiTnJ-CCaUUowhNwepBqY5A7ca-NQEOXtnQOq2GxlmobAl1O4bB-MbW0FXwww7QG236wXkYmtqq1gXXbTfX3o31Gr4rjc_BSaXaYC72dQZWT4-rxUuyfHt-XdwvE025GBJdIm2IwZSmJUOKVSijpKyKghUIs6wsiSA4M5wJpDRFQmCiaUpYbIiUGzoDdzvZfiw6U2pjo_1W9r7plP-WTjXy_8Q2a1m7L8kFQxizKHC9F_DuczRhkF0TtGlbZY0bgyQpjy_MhcgjerNDtXcheFMdzmAktynImILcpRDhq7_GDujv2-kPQHuDvA</recordid><startdate>20210125</startdate><enddate>20210125</enddate><creator>Cristobal, Carlo D</creator><creator>Ye, Qi</creator><creator>Jo, Juyeon</creator><creator>Ding, Xiaoyun</creator><creator>Wang, Chih-Yen</creator><creator>Cortes, Diego</creator><creator>Chen, Zheng</creator><creator>Lee, Hyun Kyoung</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/0000-0001-5793-4398</orcidid></search><sort><creationdate>20210125</creationdate><title>Daam2 couples translocation and clustering of Wnt receptor signalosomes through Rac1</title><author>Cristobal, Carlo D ; Ye, Qi ; Jo, Juyeon ; Ding, Xiaoyun ; Wang, Chih-Yen ; Cortes, Diego ; Chen, Zheng ; Lee, Hyun Kyoung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-cd0ce2e1334d60a6f0532dfbb6b0165dd28215e7680ac308812c3426768847e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Carrier Proteins</topic><topic>Cell Line</topic><topic>Chickens</topic><topic>Cluster Analysis</topic><topic>Haplorhini</topic><topic>Humans</topic><topic>Mice</topic><topic>Microfilament Proteins</topic><topic>Phosphorylation</topic><topic>rac1 GTP-Binding Protein - genetics</topic><topic>rac1 GTP-Binding Protein - metabolism</topic><topic>rho GTP-Binding Proteins</topic><topic>Spinal Cord - metabolism</topic><topic>Wnt Signaling Pathway</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cristobal, Carlo D</creatorcontrib><creatorcontrib>Ye, Qi</creatorcontrib><creatorcontrib>Jo, Juyeon</creatorcontrib><creatorcontrib>Ding, Xiaoyun</creatorcontrib><creatorcontrib>Wang, Chih-Yen</creatorcontrib><creatorcontrib>Cortes, Diego</creatorcontrib><creatorcontrib>Chen, Zheng</creatorcontrib><creatorcontrib>Lee, Hyun Kyoung</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>Cristobal, Carlo D</au><au>Ye, Qi</au><au>Jo, Juyeon</au><au>Ding, Xiaoyun</au><au>Wang, Chih-Yen</au><au>Cortes, Diego</au><au>Chen, Zheng</au><au>Lee, Hyun Kyoung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Daam2 couples translocation and clustering of Wnt receptor signalosomes through Rac1</atitle><jtitle>Journal of cell science</jtitle><addtitle>J Cell Sci</addtitle><date>2021-01-25</date><risdate>2021</risdate><volume>134</volume><issue>2</issue><issn>0021-9533</issn><eissn>1477-9137</eissn><abstract>Wnt signaling plays a critical role in development across species and is dysregulated in a host of human diseases. 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-PIP5K axis through its association with Rac1. Clustering of Daam2-mediated Wnt receptor complexes requires both Rac1 and PIP5K, and PIP5K promotes membrane localization of these complexes in a Rac1-dependent manner. Importantly, the localization of Daam2 complexes and Daam2-mediated canonical Wnt signaling is dependent upon actin polymerization. These studies - in chick spinal cord and human and monkey cell lines - highlight novel roles for Rac1 and the actin cytoskeleton in the regulation of canonical Wnt signaling and define Daam2 as a key scaffolding hub that coordinates membrane translocation and signalosome clustering.</abstract><cop>England</cop><pub>The Company of Biologists Ltd</pub><pmid>33310913</pmid><doi>10.1242/jcs.251140</doi><orcidid>https://orcid.org/0000-0001-5793-4398</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Company of Biologists |
| subjects | Animals Carrier Proteins Cell Line Chickens Cluster Analysis Haplorhini Humans Mice Microfilament Proteins Phosphorylation rac1 GTP-Binding Protein - genetics rac1 GTP-Binding Protein - metabolism rho GTP-Binding Proteins Spinal Cord - metabolism Wnt Signaling Pathway |
| title | Daam2 couples translocation and clustering of Wnt receptor signalosomes through Rac1 |
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