Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration
Summary: In collective cell migration, directional protrusions orient cells in response to external cues, which requires coordinated polarity among the migrating cohort. However, the molecular mechanism has not been well defined. Drosophila border cells (BCs) migrate collectively and invade via the...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471830144X |
| _version_ | 1818316498581585920 |
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| author | Yu-Chiuan Chang Jhen-Wei Wu Yi-Chi Hsieh Tzu-Han Huang Zih-Min Liao Yi-Shan Huang James A. Mondo Denise Montell Anna C.-C. Jang |
| author_facet | Yu-Chiuan Chang Jhen-Wei Wu Yi-Chi Hsieh Tzu-Han Huang Zih-Min Liao Yi-Shan Huang James A. Mondo Denise Montell Anna C.-C. Jang |
| author_sort | Yu-Chiuan Chang |
| collection | DOAJ |
| description | Summary: In collective cell migration, directional protrusions orient cells in response to external cues, which requires coordinated polarity among the migrating cohort. However, the molecular mechanism has not been well defined. Drosophila border cells (BCs) migrate collectively and invade via the confined space between nurse cells, offering an in vivo model to examine how group polarity is organized. Here, we show that the front/back polarity of BCs requires Rap1, hyperactivation of which disrupts cluster polarity and induces misoriented protrusions and loss of asymmetry in the actin network. Conversely, hypoactive Rap1 causes fewer protrusions and cluster spinning during migration. A forward genetic screen revealed that downregulation of the Hippo (Hpo) pathway core components hpo or mats enhances the Rap1V12-induced migration defect and misdirected protrusions. Mechanistically, association of Rap1V12 with the kinase domain of Hpo suppresses its activity, which releases Hpo signaling-mediated suppression of F-actin elongation, promoting cellular protrusions in collective cell migration. |
| first_indexed | 2024-12-13T09:22:23Z |
| format | Article |
| id | doaj.art-4f44a24eeccf4bc486ad42ffeeacb863 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T09:22:23Z |
| publishDate | 2018-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4f44a24eeccf4bc486ad42ffeeacb8632022-12-21T23:52:43ZengElsevierCell Reports2211-12472018-02-012282160217510.1016/j.celrep.2018.01.080Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell MigrationYu-Chiuan Chang0Jhen-Wei Wu1Yi-Chi Hsieh2Tzu-Han Huang3Zih-Min Liao4Yi-Shan Huang5James A. Mondo6Denise Montell7Anna C.-C. Jang8Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, 1 University Rd., Tainan City 701, Taiwan, Republic of China; Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, Republic of ChinaDepartment of Biotechnology and Bioindustry Sciences, National Cheng Kung University, 1 University Rd., Tainan City 701, Taiwan, Republic of ChinaDepartment of Biotechnology and Bioindustry Sciences, National Cheng Kung University, 1 University Rd., Tainan City 701, Taiwan, Republic of ChinaDepartment of Biotechnology and Bioindustry Sciences, National Cheng Kung University, 1 University Rd., Tainan City 701, Taiwan, Republic of ChinaDepartment of Biotechnology and Bioindustry Sciences, National Cheng Kung University, 1 University Rd., Tainan City 701, Taiwan, Republic of ChinaDepartment of Biotechnology and Bioindustry Sciences, National Cheng Kung University, 1 University Rd., Tainan City 701, Taiwan, Republic of ChinaDepartment of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USADepartment of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USADepartment of Biotechnology and Bioindustry Sciences, National Cheng Kung University, 1 University Rd., Tainan City 701, Taiwan, Republic of China; Corresponding authorSummary: In collective cell migration, directional protrusions orient cells in response to external cues, which requires coordinated polarity among the migrating cohort. However, the molecular mechanism has not been well defined. Drosophila border cells (BCs) migrate collectively and invade via the confined space between nurse cells, offering an in vivo model to examine how group polarity is organized. Here, we show that the front/back polarity of BCs requires Rap1, hyperactivation of which disrupts cluster polarity and induces misoriented protrusions and loss of asymmetry in the actin network. Conversely, hypoactive Rap1 causes fewer protrusions and cluster spinning during migration. A forward genetic screen revealed that downregulation of the Hippo (Hpo) pathway core components hpo or mats enhances the Rap1V12-induced migration defect and misdirected protrusions. Mechanistically, association of Rap1V12 with the kinase domain of Hpo suppresses its activity, which releases Hpo signaling-mediated suppression of F-actin elongation, promoting cellular protrusions in collective cell migration.http://www.sciencedirect.com/science/article/pii/S221112471830144XBorder cellsgroup polarityHippo signalingRap1 |
| spellingShingle | Yu-Chiuan Chang Jhen-Wei Wu Yi-Chi Hsieh Tzu-Han Huang Zih-Min Liao Yi-Shan Huang James A. Mondo Denise Montell Anna C.-C. Jang Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration Cell Reports Border cells group polarity Hippo signaling Rap1 |
| title | Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration |
| title_full | Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration |
| title_fullStr | Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration |
| title_full_unstemmed | Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration |
| title_short | Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration |
| title_sort | rap1 negatively regulates the hippo pathway to polarize directional protrusions in collective cell migration |
| topic | Border cells group polarity Hippo signaling Rap1 |
| url | http://www.sciencedirect.com/science/article/pii/S221112471830144X |
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