Arp2/3-Branched Actin Maintains an Active Pool of GTP-RhoA and Controls RhoA Abundance
Small GTPases regulate cytoskeletal dynamics, cell motility, and division under precise spatiotemporal control. Different small GTPases exhibit cross talks to exert feedback response or to act in concert during signal transduction. However, whether and how specific cytoskeletal components’...
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MDPI AG
2019-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/10/1264 |
| _version_ | 1797714649910607872 |
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| author | Yuxing Huang Xin Yi Chenlu Kang Congying Wu |
| author_facet | Yuxing Huang Xin Yi Chenlu Kang Congying Wu |
| author_sort | Yuxing Huang |
| collection | DOAJ |
| description | Small GTPases regulate cytoskeletal dynamics, cell motility, and division under precise spatiotemporal control. Different small GTPases exhibit cross talks to exert feedback response or to act in concert during signal transduction. However, whether and how specific cytoskeletal components’ feedback to upstream signaling factors remains largely elusive. Here, we report an intriguing finding that disruption of the Arp2/3-branched actin specifically reduces RhoA activity but upregulates its total protein abundance. We further dissect the mechanisms underlying these circumstances and identify the altered cortactin/p190RhoGAP interaction and weakened CCM2/Smurf1 binding to be involved in GTP-RhoA reduction and total RhoA increase, respectively. Moreover, we find that cytokinesis defects induced by Arp2/3 inhibition can be rescued by activating RhoA. Our study reveals an intricate feedback from the actin cytoskeleton to the small GTPase. Our work highlights the role of Arp2/3-branched actin in signal transduction aside from its function in serving as critical cytoskeletal components to maintain cell morphology and motility. |
| first_indexed | 2024-03-12T07:55:05Z |
| format | Article |
| id | doaj.art-954304b05a9b46e6a45848a68f5a0453 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:55:05Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-954304b05a9b46e6a45848a68f5a04532023-09-02T20:16:34ZengMDPI AGCells2073-44092019-10-01810126410.3390/cells8101264cells8101264Arp2/3-Branched Actin Maintains an Active Pool of GTP-RhoA and Controls RhoA AbundanceYuxing Huang0Xin Yi1Chenlu Kang2Congying Wu3Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, ChinaInstitute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, ChinaInstitute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, ChinaInstitute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, ChinaSmall GTPases regulate cytoskeletal dynamics, cell motility, and division under precise spatiotemporal control. Different small GTPases exhibit cross talks to exert feedback response or to act in concert during signal transduction. However, whether and how specific cytoskeletal components’ feedback to upstream signaling factors remains largely elusive. Here, we report an intriguing finding that disruption of the Arp2/3-branched actin specifically reduces RhoA activity but upregulates its total protein abundance. We further dissect the mechanisms underlying these circumstances and identify the altered cortactin/p190RhoGAP interaction and weakened CCM2/Smurf1 binding to be involved in GTP-RhoA reduction and total RhoA increase, respectively. Moreover, we find that cytokinesis defects induced by Arp2/3 inhibition can be rescued by activating RhoA. Our study reveals an intricate feedback from the actin cytoskeleton to the small GTPase. Our work highlights the role of Arp2/3-branched actin in signal transduction aside from its function in serving as critical cytoskeletal components to maintain cell morphology and motility.https://www.mdpi.com/2073-4409/8/10/1264arp2/3 complexbranched actinrhoaubiquitinationsmurf1cytokinesis |
| spellingShingle | Yuxing Huang Xin Yi Chenlu Kang Congying Wu Arp2/3-Branched Actin Maintains an Active Pool of GTP-RhoA and Controls RhoA Abundance Cells arp2/3 complex branched actin rhoa ubiquitination smurf1 cytokinesis |
| title | Arp2/3-Branched Actin Maintains an Active Pool of GTP-RhoA and Controls RhoA Abundance |
| title_full | Arp2/3-Branched Actin Maintains an Active Pool of GTP-RhoA and Controls RhoA Abundance |
| title_fullStr | Arp2/3-Branched Actin Maintains an Active Pool of GTP-RhoA and Controls RhoA Abundance |
| title_full_unstemmed | Arp2/3-Branched Actin Maintains an Active Pool of GTP-RhoA and Controls RhoA Abundance |
| title_short | Arp2/3-Branched Actin Maintains an Active Pool of GTP-RhoA and Controls RhoA Abundance |
| title_sort | arp2 3 branched actin maintains an active pool of gtp rhoa and controls rhoa abundance |
| topic | arp2/3 complex branched actin rhoa ubiquitination smurf1 cytokinesis |
| url | https://www.mdpi.com/2073-4409/8/10/1264 |
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