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The biochemical mechanism of Rho GTPase membrane binding, activation and retention in activity patterning

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Název: The biochemical mechanism of Rho GTPase membrane binding, activation and retention in activity patterning
Autoři: Michael C Armstrong, Yannic R Weiß, Lila E Hoachlander-Hobby, Ankit A Roy, Ilaria Visco, Alison Moe, Adriana E Golding, Scott D Hansen, William M Bement, Peter Bieling
Zdroj: EMBO J
Armstrong, M C, Weiß, Y R, Hoachlander-Hobby, L E, Roy, A A, Visco, I, Moe, A, Golding, A E, Hansen, S D, Bement, W M & Bieling, P 2025, ' The biochemical mechanism of Rho GTPase membrane binding, activation and retention in activity patterning ', The EMBO journal, vol. 44, no. 9, 71, pp. 2620-2657 . https://doi.org/10.1038/s44318-025-00418-z
Informace o vydavateli: Springer Science and Business Media LLC, 2025.
Rok vydání: 2025
Témata: Guanine Nucleotide Exchange Factors/metabolism, rho GTP-Binding Proteins, Cell Membrane/metabolism, Cell Membrane, GTPase-Activating Proteins, GTPase-Activating Proteins/metabolism, Guanine Nucleotide Dissociation Inhibitors/metabolism, Article, Enzyme Activation, rho GTP-Binding Proteins/metabolism, Guanine Nucleotide Exchange Factors, Humans, Animals, Protein Binding, Guanine Nucleotide Dissociation Inhibitors
Popis: Rho GTPases form plasma membrane-associated patterns that control the cytoskeleton during cell division, morphogenesis, migration, and wound repair. Their patterning involves transitions between inactive cytosolic and active membrane-bound states, regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and guanine nucleotide dissociation inhibitors (GDIs). However, the relationships between these transitions and role of different regulators remain unclear. We developed a novel reconstitution approach to study Rho GTPase patterning with all major GTPase regulators in a biochemically defined system. We show that Rho GTPase dissociation from RhoGDI is rate-limiting for its membrane association. Rho GTPase activation occurs after membrane insertion, which is unaffected by GEF activity. Once activated, Rho GTPases are retained at the membrane through effector interactions, essential for their enrichment at activation sites. Thus, high cytosolic levels of RhoGDI-bound GTPases ensure a constant supply of inactive GTPases for the membrane, where GEF-mediated activation and effector binding stabilize them. These results delineate the route by which Rho GTPase patterns are established and define stage-dependent roles of its regulators.
Druh dokumentu: Article
Other literature type
Popis souboru: application/pdf
Jazyk: English
ISSN: 1460-2075
DOI: 10.1038/s44318-025-00418-z
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/40164947
https://kclpure.kcl.ac.uk/ws/files/344447849/armstrong-et-al-the-biochemical-mechanism-of-rho-gtpase-membrane-binding-activation-and-retention-in-activity-patterning.pdf
Rights: CC BY
URL: http://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) . Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.
Přístupové číslo: edsair.doi.dedup.....2e33a06f37be1b24c1ca4806a5afd22c
Databáze: OpenAIRE
Popis
Abstrakt:Rho GTPases form plasma membrane-associated patterns that control the cytoskeleton during cell division, morphogenesis, migration, and wound repair. Their patterning involves transitions between inactive cytosolic and active membrane-bound states, regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and guanine nucleotide dissociation inhibitors (GDIs). However, the relationships between these transitions and role of different regulators remain unclear. We developed a novel reconstitution approach to study Rho GTPase patterning with all major GTPase regulators in a biochemically defined system. We show that Rho GTPase dissociation from RhoGDI is rate-limiting for its membrane association. Rho GTPase activation occurs after membrane insertion, which is unaffected by GEF activity. Once activated, Rho GTPases are retained at the membrane through effector interactions, essential for their enrichment at activation sites. Thus, high cytosolic levels of RhoGDI-bound GTPases ensure a constant supply of inactive GTPases for the membrane, where GEF-mediated activation and effector binding stabilize them. These results delineate the route by which Rho GTPase patterns are established and define stage-dependent roles of its regulators.
ISSN:14602075
DOI:10.1038/s44318-025-00418-z