Academic Journal
The guanine exchange factor SWAP70 mediates vGPCR-induced endothelial plasticity
| العنوان: | The guanine exchange factor SWAP70 mediates vGPCR-induced endothelial plasticity |
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| المؤلفون: | Dwyer, Julie, Azzi, Sandy, Leclair, Héloïse, M, Georges, Steven, Carlotti, Agnès, Treps, Lucas, Galan-Moya, Eva, M, Alexia, Catherine, Dupin, Nicolas, Bidère, Nicolas, Gavard, Julie |
| المساهمون: | Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Pathologie, Hôpital Cochin AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cytokines et Immunologie des Tumeurs Humaines (U753), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie |
| المصدر: | EISSN: 1478-811X ; Cell Communication and Signaling ; https://inserm.hal.science/inserm-01264495 ; Cell Communication and Signaling, 2015, 13 (1), pp.11. ⟨10.1186/s12964-015-0090-1⟩ |
| بيانات النشر: | HAL CCSD |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Angiogenesis, Human herpes virus 8, Kaposi sarcoma herpes virus, Permeability, Rac, Small GTPases, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; AbstractBackgroundThe viral G protein-coupled receptor (vGPCR) is proposed to act as one of the predominant mediators of Kaposi’s sarcoma (KS), a human herpes virus 8 (HHV8)-elicited disease. The actions of vGPCR manifest pathogenesis, in part, through increased permeability of endothelial cells. Endothelial cell-cell junctions have indeed emerged as an instrumental target involved in the vasculature defects observed within the tumor microenvironment. The pathway leading to adherens junction destabilization has been shown to involve the activation of the small GTPase Rac, in the context of either latent infection or the sole expression of vGPCR. However, the precise molecular mechanisms governed by vGPCR in vascular leakage require further elucidation.FindingsGuanine exchange factors (GEFs) function as critical molecular switches that control the activation of small GTPases. We therefore screened the effects of 80 siRNAs targeting GEFs on vGPCR-driven endothelial permeability and identified switch-associated protein 70 (SWAP70) as necessary for its elevating effects. Pull-down experiments further showed that Rac activation by vGPCR was dependent on SWAP70. Examination of tissues and cells from HHV8-positive patients revealed that SWAP70 was ubiquitously expressed. Furthermore, SWAP70 was found to be crucial for vGPCR-driven endothelial tube formation and endothelial sprouting in vitro.ConclusionsSWAP70 appears to act as a molecular intermediate between vGPCR and endothelial activation. Because of the important role of vGPCR-mediated endothelial plasticity in KS pathogenesis, inhibition of SWAP70 function could be of interest for blocking vGPCR-driven activities in HHV8-defined diseases. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | inserm-01264495; https://inserm.hal.science/inserm-01264495; https://inserm.hal.science/inserm-01264495/document; https://inserm.hal.science/inserm-01264495/file/12964_2015_Article_90.pdf; https://inserm.hal.science/inserm-01264495/file/12964_2015_90_MOESM2_ESM.pdf; https://inserm.hal.science/inserm-01264495/file/12964_2015_90_MOESM3_ESM.pdf |
| DOI: | 10.1186/s12964-015-0090-1 |
| الاتاحة: | https://inserm.hal.science/inserm-01264495 https://inserm.hal.science/inserm-01264495/document https://inserm.hal.science/inserm-01264495/file/12964_2015_Article_90.pdf https://inserm.hal.science/inserm-01264495/file/12964_2015_90_MOESM2_ESM.pdf https://inserm.hal.science/inserm-01264495/file/12964_2015_90_MOESM3_ESM.pdf https://doi.org/10.1186/s12964-015-0090-1 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.C8DFBE65 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12964-015-0090-1 |
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