The guanine exchange factor SWAP70 mediates vGPCR-induced endothelial plasticity - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Cell Communication and Signaling Year : 2015

The guanine exchange factor SWAP70 mediates vGPCR-induced endothelial plasticity

Julie Dwyer
  • Function : Author
  • PersonId : 975707
Sandy Azzi
  • Function : Author
  • PersonId : 942065
Héloïse M Leclair
  • Function : Author
  • PersonId : 941124
Steven Georges
  • Function : Author
  • PersonId : 975708
Agnès Carlotti
  • Function : Author
  • PersonId : 975709
Lucas Treps
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  • PersonId : 975710
Eva M Galan-Moya
  • Function : Author
  • PersonId : 976667
Nicolas Dupin
  • Function : Author
  • PersonId : 975711
Nicolas Bidère
  • Function : Author
  • PersonId : 861533
Julie Gavard
  • Function : Correspondent author
  • PersonId : 855795

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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.
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Origin : Publication funded by an institution
Origin : Publication funded by an institution
Origin : Publication funded by an institution

Dates and versions

inserm-01264495 , version 1 (29-01-2016)



Julie Dwyer, Sandy Azzi, Héloïse M Leclair, Steven Georges, Agnès Carlotti, et al.. The guanine exchange factor SWAP70 mediates vGPCR-induced endothelial plasticity. Cell Communication and Signaling, 2015, 13 (1), pp.11. ⟨10.1186/s12964-015-0090-1⟩. ⟨inserm-01264495⟩
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