دورية أكاديمية
أعرض في EDS

A computational analysis of the role of integrins and Rho-GTPases in the emergence and disruption of apical-basal polarization in renal epithelial cells.

التفاصيل البيبلوغرافية
العنوان: A computational analysis of the role of integrins and Rho-GTPases in the emergence and disruption of apical-basal polarization in renal epithelial cells.
المؤلفون: Hagelaars MJ; Eindhoven University of Technology, Department of Biomedical Engineering, Eindhoven, The Netherlands.; Institute for Complex Molecular Systems, Eindhoven, The Netherlands., Nikolic M; Eindhoven University of Technology, Department of Biomedical Engineering, Eindhoven, The Netherlands.; Institute for Complex Molecular Systems, Eindhoven, The Netherlands., Vermeulen M; Eindhoven University of Technology, Department of Biomedical Engineering, Eindhoven, The Netherlands., Dekker S; Eindhoven University of Technology, Department of Biomedical Engineering, Eindhoven, The Netherlands., Bouten CVC; Eindhoven University of Technology, Department of Biomedical Engineering, Eindhoven, The Netherlands.; Institute for Complex Molecular Systems, Eindhoven, The Netherlands., Loerakker S; Eindhoven University of Technology, Department of Biomedical Engineering, Eindhoven, The Netherlands.; Institute for Complex Molecular Systems, Eindhoven, The Netherlands.
المصدر: PLoS computational biology [PLoS Comput Biol] 2024 May 20; Vol. 20 (5), pp. e1012140. Date of Electronic Publication: 2024 May 20 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238922 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7358 (Electronic) Linking ISSN: 1553734X NLM ISO Abbreviation: PLoS Comput Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, [2005]-
مواضيع طبية MeSH: Cell Polarity*/physiology , Integrins*/metabolism , Epithelial Cells*/metabolism , rho GTP-Binding Proteins*/metabolism , Kidney*/metabolism , Kidney*/cytology, Animals ; Computational Biology ; Models, Biological ; Computer Simulation ; Humans ; Epithelial-Mesenchymal Transition/physiology
مستخلص: Apical-basal polarization in renal epithelial cells is crucial to renal function and an important trigger for tubule formation in kidney development. Loss of polarity can induce epithelial-to-mesenchymal transition (EMT), which can lead to kidney pathologies. Understanding the relative and combined roles of the involved proteins and their interactions that govern epithelial polarity may provide insights for controlling the process of polarization via chemical or mechanical manipulations in an in vitro or in vivo setting. Here, we developed a computational framework that integrates several known interactions between integrins, Rho-GTPases Rho, Rac and Cdc42, and polarity complexes Par and Scribble, to study their mutual roles in the emergence of polarization. The modeled protein interactions were shown to induce the emergence of polarized distributions of Rho-GTPases, which in turn led to the accumulation of apical and basal polarity complexes Par and Scribble at their respective poles, effectively recapitulating polarization. Our multiparametric sensitivity analysis suggested that polarization depends foremost on the mutual inhibition between Rac and Rho. Next, we used the computational framework to investigate the role of integrins and GTPases in the generation and disruption of polarization. We found that a minimum concentration of integrins is required to catalyze the process of polarization. Furthermore, loss of polarization was found to be only inducible via complete degradation of the Rho-GTPases Rho and Cdc42, suggesting that polarization is fairly stable once it is established. Comparison of our computational predictions against data from in vitro experiments in which we induced EMT in renal epithelial cells while quantifying the relative Rho-GTPase levels, displayed that EMT coincides with a large reduction in the Rho-GTPase Rho. Collectively, these results demonstrate the essential roles of integrins and Rho-GTPases in the establishment and disruption of apical-basal polarity and thereby provide handles for the in vitro or in vivo regulation of polarity.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Hagelaars et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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المشرفين على المادة: 0 (Integrins)
EC 3.6.5.2 (rho GTP-Binding Proteins)
تواريخ الأحداث: Date Created: 20240520 Date Completed: 20240531 Latest Revision: 20240603
رمز التحديث: 20240603
مُعرف محوري في PubMed: PMC11142725
DOI: 10.1371/journal.pcbi.1012140
PMID: 38768266
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7358
DOI:10.1371/journal.pcbi.1012140