AAMP and MTSS1 Are Novel Negative Regulators of Endothelial Barrier Function Identified in a Proteomics Screen
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| Název: | AAMP and MTSS1 Are Novel Negative Regulators of Endothelial Barrier Function Identified in a Proteomics Screen |
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| Autoři: | Fabienne Podieh, Max C. Overboom, Jaco C. Knol, Sander R. Piersma, Richard Goeij-de Haas, Thang V. Pham, Connie R. Jimenez, Peter L. Hordijk |
| Zdroj: | Cells Cells, Vol 13, Iss 19, p 1609 (2024) |
| Informace o vydavateli: | MDPI AG, 2024. |
| Rok vydání: | 2024 |
| Témata: | Proteomics, Microfilament Proteins/metabolism, Endothelial Cells/metabolism, Article, Cortactin/metabolism, Capillary Permeability, rhoA GTP-Binding Protein/metabolism, ubiquitin, Rho GTPases, Human Umbilical Vein Endothelial Cells, Humans, rhoB GTP-Binding Protein, Human Umbilical Vein Endothelial Cells/metabolism, QH573-671, protein turnover, Microfilament Proteins, rhoB GTP-Binding Protein/metabolism, Ubiquitination, Endothelial Cells, endothelial cells, Actins, Actins/metabolism, Proteomics/methods, Cytology, rhoA GTP-Binding Protein, Cortactin, monolayer integrity |
| Popis: | Cell–cell adhesion in endothelial monolayers is tightly controlled and crucial for vascular integrity. Recently, we reported on the importance of fast protein turnover for maintenance of endothelial barrier function. Specifically, continuous ubiquitination and degradation of the Rho GTPase RhoB is crucial to preserve quiescent endothelial integrity. Here, we sought to identify other barrier regulators, which are characterized by a short half-life, using a proteomics approach. Following short-term inhibition of ubiquitination with E1 ligase inhibitor MLN7243 or Cullin E3 ligase inhibitor MLN4924 in primary human endothelial cells, we identified sixty significantly differentially expressed proteins. Intriguingly, our data showed that AAMP and MTSS1 are novel negative regulators of endothelial barrier function and that their turnover is tightly controlled by ubiquitination. Mechanistically, AAMP regulates the stability and activity of RhoA and RhoB, and colocalizes with F-actin and cortactin at membrane ruffles, possibly regulating F-actin dynamics. Taken together, these findings demonstrate the critical role of protein turnover of specific proteins in the regulation of endothelial barrier function, contributing to our options to target dysregulation of vascular permeability. |
| Druh dokumentu: | Article Other literature type |
| Jazyk: | English |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells13191609 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/39404373 https://doaj.org/article/80f2bfadc11645b6aa1d1963fc5fbf74 https://pure.amsterdamumc.nl/en/publications/ef5658a1-5c24-4f11-89af-1c53acfbcaf1 https://doi.org/10.3390/cells13191609 |
| Rights: | CC BY |
| Přístupové číslo: | edsair.doi.dedup.....cd7da2c1bc626bd6875a8e178d1f1fff |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Cell–cell adhesion in endothelial monolayers is tightly controlled and crucial for vascular integrity. Recently, we reported on the importance of fast protein turnover for maintenance of endothelial barrier function. Specifically, continuous ubiquitination and degradation of the Rho GTPase RhoB is crucial to preserve quiescent endothelial integrity. Here, we sought to identify other barrier regulators, which are characterized by a short half-life, using a proteomics approach. Following short-term inhibition of ubiquitination with E1 ligase inhibitor MLN7243 or Cullin E3 ligase inhibitor MLN4924 in primary human endothelial cells, we identified sixty significantly differentially expressed proteins. Intriguingly, our data showed that AAMP and MTSS1 are novel negative regulators of endothelial barrier function and that their turnover is tightly controlled by ubiquitination. Mechanistically, AAMP regulates the stability and activity of RhoA and RhoB, and colocalizes with F-actin and cortactin at membrane ruffles, possibly regulating F-actin dynamics. Taken together, these findings demonstrate the critical role of protein turnover of specific proteins in the regulation of endothelial barrier function, contributing to our options to target dysregulation of vascular permeability. |
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| ISSN: | 20734409 |
| DOI: | 10.3390/cells13191609 |