NRas activity is regulated by dynamic interactions with nanoscale signaling clusters at the plasma membrane
Summary: NRas is a key mediator of the mitogenic pathway in normal cells and in cancer cells. Its dynamics and nanoscale organization at the plasma membrane (PM) facilitate its signaling. Here, we used two-color photoactivated localization microscopy to resolve the organization of individual NRas an...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222015541 |
| _version_ | 1828096212284211200 |
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| author | Oren Yakovian Julia Sajman Michal Alon Rand Arafeh Yardena Samuels Eilon Sherman |
| author_facet | Oren Yakovian Julia Sajman Michal Alon Rand Arafeh Yardena Samuels Eilon Sherman |
| author_sort | Oren Yakovian |
| collection | DOAJ |
| description | Summary: NRas is a key mediator of the mitogenic pathway in normal cells and in cancer cells. Its dynamics and nanoscale organization at the plasma membrane (PM) facilitate its signaling. Here, we used two-color photoactivated localization microscopy to resolve the organization of individual NRas and associated signaling proteins in live melanoma cells, with resolution down to ∼20 nm. Upon EGF activation, a fraction of NRas and BRAF (dis)assembled synchronously at the PM in co-clusters. NRas and BRAF clusters associated with GPI-enriched domains, serving as possible nucleation sites for these clusters. NRas and BRAF association in mutual clusters was reduced by the NRas farnesylation inhibitor lonafarnib, yet enhanced by the BRAF inhibitor vemurafenib. Surprisingly, dispersed NRas molecules associated with the periphery of self-clusters of either Grb2 or NF1. Thus, NRas-mediated signaling, which is critical in health and disease, is regulated by dynamic interactions with functional clusters of BRAF or other related proteins at the PM. |
| first_indexed | 2024-04-11T07:25:41Z |
| format | Article |
| id | doaj.art-bee7726ca2f3415bb0694501caa074a0 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-11T07:25:41Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-bee7726ca2f3415bb0694501caa074a02022-12-22T04:37:04ZengElsevieriScience2589-00422022-11-012511105282NRas activity is regulated by dynamic interactions with nanoscale signaling clusters at the plasma membraneOren Yakovian0Julia Sajman1Michal Alon2Rand Arafeh3Yardena Samuels4Eilon Sherman5Racah Institute of Physics, The Hebrew University, Jerusalem 91904, IsraelRacah Institute of Physics, The Hebrew University, Jerusalem 91904, IsraelDepartment of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, IsraelDepartment of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel; Department of Molecular Oncology, Dana Farber Cancer Institute, Boston, MA, USADepartment of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, IsraelRacah Institute of Physics, The Hebrew University, Jerusalem 91904, Israel; Corresponding authorSummary: NRas is a key mediator of the mitogenic pathway in normal cells and in cancer cells. Its dynamics and nanoscale organization at the plasma membrane (PM) facilitate its signaling. Here, we used two-color photoactivated localization microscopy to resolve the organization of individual NRas and associated signaling proteins in live melanoma cells, with resolution down to ∼20 nm. Upon EGF activation, a fraction of NRas and BRAF (dis)assembled synchronously at the PM in co-clusters. NRas and BRAF clusters associated with GPI-enriched domains, serving as possible nucleation sites for these clusters. NRas and BRAF association in mutual clusters was reduced by the NRas farnesylation inhibitor lonafarnib, yet enhanced by the BRAF inhibitor vemurafenib. Surprisingly, dispersed NRas molecules associated with the periphery of self-clusters of either Grb2 or NF1. Thus, NRas-mediated signaling, which is critical in health and disease, is regulated by dynamic interactions with functional clusters of BRAF or other related proteins at the PM.http://www.sciencedirect.com/science/article/pii/S2589004222015541Biological sciencesCell biologyBiophysicsMolecular biology |
| spellingShingle | Oren Yakovian Julia Sajman Michal Alon Rand Arafeh Yardena Samuels Eilon Sherman NRas activity is regulated by dynamic interactions with nanoscale signaling clusters at the plasma membrane iScience Biological sciences Cell biology Biophysics Molecular biology |
| title | NRas activity is regulated by dynamic interactions with nanoscale signaling clusters at the plasma membrane |
| title_full | NRas activity is regulated by dynamic interactions with nanoscale signaling clusters at the plasma membrane |
| title_fullStr | NRas activity is regulated by dynamic interactions with nanoscale signaling clusters at the plasma membrane |
| title_full_unstemmed | NRas activity is regulated by dynamic interactions with nanoscale signaling clusters at the plasma membrane |
| title_short | NRas activity is regulated by dynamic interactions with nanoscale signaling clusters at the plasma membrane |
| title_sort | nras activity is regulated by dynamic interactions with nanoscale signaling clusters at the plasma membrane |
| topic | Biological sciences Cell biology Biophysics Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222015541 |
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