Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration

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

研究成果: Article

4 引文 (Scopus)

摘要

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 Rap1 V12 -induced migration defect and misdirected protrusions. Mechanistically, association of Rap1 V12 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. In collective cell movement, coordinated polarity among the migrating cohort is required for directional protrusions in response to external cues. Chang et al. show that such group polarity requires Rap1 activity, which promotes cellular protrusions and gives cells an advantage in competing to lead the cluster.

原文English
頁(從 - 到)2160-2175
頁數16
期刊Cell Reports
22
發行號8
DOIs
出版狀態Published - 2018 二月 20

指紋

Cell Movement
Actins
Cell Surface Extensions
Cues
Elongation
Phosphotransferases
Confined Spaces
Cells
Cell Polarity
Defects
Drosophila
Down-Regulation
Nurses

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

引用此文

Chang, Yu Chiuan ; Wu, Jhen Wei ; Hsieh, Yi Chi ; Huang, Tzu Han ; Liao, Zih Min ; Huang, Yi Shan ; Mondo, James A. ; Montell, Denise ; Jang, Anna C.C. / Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration. 於: Cell Reports. 2018 ; 卷 22, 編號 8. 頁 2160-2175.
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abstract = "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 Rap1 V12 -induced migration defect and misdirected protrusions. Mechanistically, association of Rap1 V12 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. In collective cell movement, coordinated polarity among the migrating cohort is required for directional protrusions in response to external cues. Chang et al. show that such group polarity requires Rap1 activity, which promotes cellular protrusions and gives cells an advantage in competing to lead the cluster.",
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Chang, YC, Wu, JW, Hsieh, YC, Huang, TH, Liao, ZM, Huang, YS, Mondo, JA, Montell, D & Jang, ACC 2018, 'Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration', Cell Reports, 卷 22, 編號 8, 頁 2160-2175. https://doi.org/10.1016/j.celrep.2018.01.080

Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration. / Chang, Yu Chiuan; Wu, Jhen Wei; Hsieh, Yi Chi; Huang, Tzu Han; Liao, Zih Min; Huang, Yi Shan; Mondo, James A.; Montell, Denise; Jang, Anna C.C.

於: Cell Reports, 卷 22, 編號 8, 20.02.2018, p. 2160-2175.

研究成果: Article

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AU - Liao, Zih Min

AU - Huang, Yi Shan

AU - Mondo, James A.

AU - Montell, Denise

AU - Jang, Anna C.C.

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