PECAM-1 supports leukocyte diapedesis by tension-dependent dephosphorylation of VE-cadherin

ABSTRACT: Leukocyte extravasation is an essential step during the immune response and requires the destabilization of endothelial junctions. We have shown previously that this process depends in vivo on the dephosphorylation of VE-cadherin-Y731. Here, we reveal the underlying mechanism. Leukocyte-induced stimulation of PECAM-1 triggers dissociation of the phosphatase SHP2 which then directly targets VE-cadherin-Y731. The binding site of PECAM-1 for SHP2 is needed for VE-cadherin dephosphorylation and subsequent endocytosis. Importantly, the contribution of PECAM-1 to leukocyte diapedesis in vitro and in vivo was strictly dependent on the presence of Y731 of VE-cadherin. In addition to SHP2, dephosphorylation of Y731 required Ca2+-signaling, non-muscle myosin II activation, and endothelial cell tensi

SUBMITTER: Mrs. Nida Arif 

PROVIDER: S-SCDT-EMBOJ-2020-106113 | biostudies-other |

REPOSITORIES: biostudies-other