RhoB plays a central role in hyperosmolarity-induced cell shrinkage in renal cells.
Rho GTP‐binding proteins
RhoB
cell volume
hyperosmolarity
kidney
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
30 Jun 2024
30 Jun 2024
Historique:
revised:
06
06
2024
received:
28
11
2023
accepted:
11
06
2024
medline:
1
7
2024
pubmed:
1
7
2024
entrez:
1
7
2024
Statut:
aheadofprint
Résumé
The small Rho GTP-binding proteins are important cell morphology, function, and apoptosis regulators. Unlike other Rho proteins, RhoB can be subjected to either geranylgeranylation (RhoB-GG) or farnesylation (RhoB-F), making that the only target of the farnesyltransferase inhibitor (FTI). Fluorescence resonance energy transfer experiments revealed that RhoB is activated by hyperosmolarity. By contrast, hyposmolarity did not affect RhoB activity. Interestingly, treatment with farnesyltransferase inhibitor-277 (FTI-277) decreased the cell size. To evaluate whether RhoB plays a role in volume reduction, renal collecting duct MCD4 cells and Human Kidney, HK-2 were transiently transfected with RhoB-wildtype-Enhance Green Fluorescence Protein (RhoB-wt-EGFP) and RhoB-CLLL-EGFP which cannot undergo farnesylation. A calcein-based fluorescent assay revealed that hyperosmolarity caused a significant reduction of cell volume in mock and RhoB-wt-EGFP-expressing cells. By contrast, cells treated with FTI-277 or expressing the RhoB-CLLL-EGFP mutant did not properly respond to hyperosmolarity with respect to mock and RhoB-wt-EGFP expressing cells. These findings were further confirmed by 3D-LSCM showing that RhoB-CLLL-EGFP cells displayed a significant reduction in cell size compared to cells expressing RhoB-wt-EGFP. Moreover, flow cytometry analysis revealed that RhoB-CLLL-EGFP expressing cells as well as FTI-277-treated cells showed a significant increase in cell apoptosis. Together, these data suggested that: (i) RhoB is sensitive to hyperosmolarity and not to hyposmolarity; (ii) inhibition of RhoB farnesylation associates with an increase in cell apoptosis, likely suggesting that RhoB might be a paramount player controlling apoptosis by interfering with responses to cell volume change.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministero dell'Università e della Ricerca
Informations de copyright
© 2024 Wiley Periodicals LLC.
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