Zyxin links fat signaling to the hippo pathway.
The Hippo signaling pathway has a conserved role in growth control and is of fundamental importance during both normal development and oncogenesis. Despite rapid progress in recent years, key steps in the pathway remain poorly understood, in part due to the incomplete identification of components. T...
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Public Library of Science (PLoS)
2011-06-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1000624&type=printable |
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| author | Cordelia Rauskolb Guohui Pan B V V G Reddy Hyangyee Oh Kenneth D Irvine |
| author_facet | Cordelia Rauskolb Guohui Pan B V V G Reddy Hyangyee Oh Kenneth D Irvine |
| author_sort | Cordelia Rauskolb |
| collection | DOAJ |
| description | The Hippo signaling pathway has a conserved role in growth control and is of fundamental importance during both normal development and oncogenesis. Despite rapid progress in recent years, key steps in the pathway remain poorly understood, in part due to the incomplete identification of components. Through a genetic screen, we identified the Drosophila Zyxin family gene, Zyx102 (Zyx), as a component of the Hippo pathway. Zyx positively regulates the Hippo pathway transcriptional co-activator Yorkie, as its loss reduces Yorkie activity and organ growth. Through epistasis tests, we position the requirement for Zyx within the Fat branch of Hippo signaling, downstream of Fat and Dco, and upstream of the Yorkie kinase Warts, and we find that Zyx is required for the influence of Fat on Warts protein levels. Zyx localizes to the sub-apical membrane, with distinctive peaks of accumulation at intercellular vertices. This partially overlaps the membrane localization of the myosin Dachs, which has similar effects on Fat-Hippo signaling. Co-immunoprecipitation experiments show that Zyx can bind to Dachs and that Dachs stimulates binding of Zyx to Warts. We also extend characterization of the Ajuba LIM protein Jub and determine that although Jub and Zyx share C-terminal LIM domains, they regulate Hippo signaling in distinct ways. Our results identify a role for Zyx in the Hippo pathway and suggest a mechanism for the role of Dachs: because Fat regulates the localization of Dachs to the membrane, where it can overlap with Zyx, we propose that the regulated localization of Dachs influences downstream signaling by modulating Zyx-Warts binding. Mammalian Zyxin proteins have been implicated in linking effects of mechanical strain to cell behavior. Our identification of Zyx as a regulator of Hippo signaling thus also raises the possibility that mechanical strain could be linked to the regulation of gene expression and growth through Hippo signaling. |
| format | Article |
| id | doaj-art-ca21977fbc5f4c3da8a2a54fb4f19da2 |
| institution | Kabale University |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2011-06-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Biology |
| spelling | doaj-art-ca21977fbc5f4c3da8a2a54fb4f19da22025-08-20T03:46:42ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852011-06-0196e100062410.1371/journal.pbio.1000624Zyxin links fat signaling to the hippo pathway.Cordelia RauskolbGuohui PanB V V G ReddyHyangyee OhKenneth D IrvineThe Hippo signaling pathway has a conserved role in growth control and is of fundamental importance during both normal development and oncogenesis. Despite rapid progress in recent years, key steps in the pathway remain poorly understood, in part due to the incomplete identification of components. Through a genetic screen, we identified the Drosophila Zyxin family gene, Zyx102 (Zyx), as a component of the Hippo pathway. Zyx positively regulates the Hippo pathway transcriptional co-activator Yorkie, as its loss reduces Yorkie activity and organ growth. Through epistasis tests, we position the requirement for Zyx within the Fat branch of Hippo signaling, downstream of Fat and Dco, and upstream of the Yorkie kinase Warts, and we find that Zyx is required for the influence of Fat on Warts protein levels. Zyx localizes to the sub-apical membrane, with distinctive peaks of accumulation at intercellular vertices. This partially overlaps the membrane localization of the myosin Dachs, which has similar effects on Fat-Hippo signaling. Co-immunoprecipitation experiments show that Zyx can bind to Dachs and that Dachs stimulates binding of Zyx to Warts. We also extend characterization of the Ajuba LIM protein Jub and determine that although Jub and Zyx share C-terminal LIM domains, they regulate Hippo signaling in distinct ways. Our results identify a role for Zyx in the Hippo pathway and suggest a mechanism for the role of Dachs: because Fat regulates the localization of Dachs to the membrane, where it can overlap with Zyx, we propose that the regulated localization of Dachs influences downstream signaling by modulating Zyx-Warts binding. Mammalian Zyxin proteins have been implicated in linking effects of mechanical strain to cell behavior. Our identification of Zyx as a regulator of Hippo signaling thus also raises the possibility that mechanical strain could be linked to the regulation of gene expression and growth through Hippo signaling.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1000624&type=printable |
| spellingShingle | Cordelia Rauskolb Guohui Pan B V V G Reddy Hyangyee Oh Kenneth D Irvine Zyxin links fat signaling to the hippo pathway. PLoS Biology |
| title | Zyxin links fat signaling to the hippo pathway. |
| title_full | Zyxin links fat signaling to the hippo pathway. |
| title_fullStr | Zyxin links fat signaling to the hippo pathway. |
| title_full_unstemmed | Zyxin links fat signaling to the hippo pathway. |
| title_short | Zyxin links fat signaling to the hippo pathway. |
| title_sort | zyxin links fat signaling to the hippo pathway |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1000624&type=printable |
| work_keys_str_mv | AT cordeliarauskolb zyxinlinksfatsignalingtothehippopathway AT guohuipan zyxinlinksfatsignalingtothehippopathway AT bvvgreddy zyxinlinksfatsignalingtothehippopathway AT hyangyeeoh zyxinlinksfatsignalingtothehippopathway AT kennethdirvine zyxinlinksfatsignalingtothehippopathway |