The tetraspanin CD151-ARSA mutant inhibits angiogenesis via the YRSL sequence

Previous studies have shown that the tetraspanin CD151 is essential forpathological or physiological angiogenesis. However, the cellular signaling mechanismand the role of the CD151 YRSL sorting motif in in vitro vasculogenesis remainsunknown. In this study, the results showed that both CD151 and CD151-ARSA genedelivery were capable of increasing the expression of CD151 at the protein levelin human umbilical vein endothelial cells (HUVECs). Moreover, there was no significantdifference in CD151 protein expression between the CD151 group and the CD151-ARSAgroup. Overexpression of CD151 promoted HUVEC cell proliferation, migration andcapillary network formation in vitro. However, in the CD151-ARSA group, the abilitiesof cell proliferation, migration and capillary network formation were all decreased,compared with the CD151 group. Furthermore, the activation of PI3K, Akt and ERKsignaling pathways was attenuated in the CD151-ARSA mutant group compared withthe CD151 group. This study suggests that the YRSL motif of CD151 plays a keyrole in CD151-induced angiogenesis. Our observations provide insights into a newmechanism of CD151 regulating angiogenesis via vesicle trafficking.