Spatiotemporal Coordination of Rac1 and Cdc42 at the Whole Cell Level during Cell Ruffling
Rho-GTPases are central regulators within a complex signaling network that controls cytoskeletal organization and cell movement. The network includes multiple GTPases, such as the most studied Rac1, Cdc42, and RhoA, along with their numerous effectors that provide mutual regulation through feedback...
| الحاوية / القاعدة: | Cells |
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| المؤلفون الرئيسيون: | , , , , |
| التنسيق: | مقال |
| اللغة: | الإنجليزية |
| منشور في: |
MDPI AG
2023-06-01
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| الموضوعات: | |
| الوصول للمادة أونلاين: | https://www.mdpi.com/2073-4409/12/12/1638 |
| _version_ | 1850416953326305280 |
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| author | Siarhei Hladyshau Jorik P. Stoop Kosei Kamada Shuyi Nie Denis Tsygankov |
| author_facet | Siarhei Hladyshau Jorik P. Stoop Kosei Kamada Shuyi Nie Denis Tsygankov |
| author_sort | Siarhei Hladyshau |
| collection | DOAJ |
| container_title | Cells |
| description | Rho-GTPases are central regulators within a complex signaling network that controls cytoskeletal organization and cell movement. The network includes multiple GTPases, such as the most studied Rac1, Cdc42, and RhoA, along with their numerous effectors that provide mutual regulation through feedback loops. Here we investigate the temporal and spatial relationship between Rac1 and Cdc42 during membrane ruffling, using a simulation model that couples GTPase signaling with cell morphodynamics and captures the GTPase behavior observed with FRET-based biosensors. We show that membrane velocity is regulated by the kinetic rate of GTPase activation rather than the concentration of active GTPase. Our model captures both uniform and polarized ruffling. We also show that cell-type specific time delays between Rac1 and Cdc42 activation can be reproduced with a single signaling motif, in which the delay is controlled by feedback from Cdc42 to Rac1. The resolution of our simulation output matches those of time-lapsed recordings of cell dynamics and GTPase activity. Our data-driven modeling approach allows us to validate simulation results with quantitative precision using the same pipeline for the analysis of simulated and experimental data. |
| format | Article |
| id | doaj-art-e4d8ccdcddbd426db6b57301483065f3 |
| institution | Directory of Open Access Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| spelling | doaj-art-e4d8ccdcddbd426db6b57301483065f32025-08-19T22:44:40ZengMDPI AGCells2073-44092023-06-011212163810.3390/cells12121638Spatiotemporal Coordination of Rac1 and Cdc42 at the Whole Cell Level during Cell RufflingSiarhei Hladyshau0Jorik P. Stoop1Kosei Kamada2Shuyi Nie3Denis Tsygankov4School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USAWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USAFaculty of Medicine, The University of Tokyo, Tokyo 113-8654, JapanSchool of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USAWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USARho-GTPases are central regulators within a complex signaling network that controls cytoskeletal organization and cell movement. The network includes multiple GTPases, such as the most studied Rac1, Cdc42, and RhoA, along with their numerous effectors that provide mutual regulation through feedback loops. Here we investigate the temporal and spatial relationship between Rac1 and Cdc42 during membrane ruffling, using a simulation model that couples GTPase signaling with cell morphodynamics and captures the GTPase behavior observed with FRET-based biosensors. We show that membrane velocity is regulated by the kinetic rate of GTPase activation rather than the concentration of active GTPase. Our model captures both uniform and polarized ruffling. We also show that cell-type specific time delays between Rac1 and Cdc42 activation can be reproduced with a single signaling motif, in which the delay is controlled by feedback from Cdc42 to Rac1. The resolution of our simulation output matches those of time-lapsed recordings of cell dynamics and GTPase activity. Our data-driven modeling approach allows us to validate simulation results with quantitative precision using the same pipeline for the analysis of simulated and experimental data.https://www.mdpi.com/2073-4409/12/12/1638multiscale modelingmorphodynamicsRho family GTPasesFRET-based biosensorscytoskeletal regulation |
| spellingShingle | Siarhei Hladyshau Jorik P. Stoop Kosei Kamada Shuyi Nie Denis Tsygankov Spatiotemporal Coordination of Rac1 and Cdc42 at the Whole Cell Level during Cell Ruffling multiscale modeling morphodynamics Rho family GTPases FRET-based biosensors cytoskeletal regulation |
| title | Spatiotemporal Coordination of Rac1 and Cdc42 at the Whole Cell Level during Cell Ruffling |
| title_full | Spatiotemporal Coordination of Rac1 and Cdc42 at the Whole Cell Level during Cell Ruffling |
| title_fullStr | Spatiotemporal Coordination of Rac1 and Cdc42 at the Whole Cell Level during Cell Ruffling |
| title_full_unstemmed | Spatiotemporal Coordination of Rac1 and Cdc42 at the Whole Cell Level during Cell Ruffling |
| title_short | Spatiotemporal Coordination of Rac1 and Cdc42 at the Whole Cell Level during Cell Ruffling |
| title_sort | spatiotemporal coordination of rac1 and cdc42 at the whole cell level during cell ruffling |
| topic | multiscale modeling morphodynamics Rho family GTPases FRET-based biosensors cytoskeletal regulation |
| url | https://www.mdpi.com/2073-4409/12/12/1638 |
| work_keys_str_mv | AT siarheihladyshau spatiotemporalcoordinationofrac1andcdc42atthewholecelllevelduringcellruffling AT jorikpstoop spatiotemporalcoordinationofrac1andcdc42atthewholecelllevelduringcellruffling AT koseikamada spatiotemporalcoordinationofrac1andcdc42atthewholecelllevelduringcellruffling AT shuyinie spatiotemporalcoordinationofrac1andcdc42atthewholecelllevelduringcellruffling AT denistsygankov spatiotemporalcoordinationofrac1andcdc42atthewholecelllevelduringcellruffling |