Opening of Cx43-formed hemichannels mediates the Ca2+ signaling associated with endothelial cell migration

Endothelial cell migration is a key process in angiogenesis. Progress of endothelial cell migration is orchestrated by coordinated generation of Ca2+ signals through a mechanism organized in caveolar microdomains. Connexins (Cx) play a central role in coordination of endothelial cell function, directly by cell-to-cell communication via gap junction and, indirectly, by the release of autocrine/paracrine signals through Cx-formed hemichannels. However, Cx hemichannels are also permeable to Ca2+ and Cx43 can be associated with caveolin-1, a structural protein of caveolae. We proposed that endothelial cell migration relies on Cx43 hemichannel opening. Here we show a novel mechanism of Ca2+ signaling in endothelial cell migration. The Ca2+ signaling that mediates endothelial cell migration and the subsequent tubular structure formation depended on Cx43 hemichannel opening and is associated with the translocation of Cx43 with caveolae to the rear part of the cells. These findings indicate that Cx43 hemichannels play a central role in endothelial cell migration and provide new therapeutic targets for the control of deregulated angiogenesis in pathological conditions such as cancer.

Automated summary

Endothelial cell migration, a crucial process in angiogenesis, is driven by coordinated generation of Ca2+ signals in caveolar microdomains. Connexins (Cx) play a central role in endothelial cell function through direct cell-to-cell communication and the release of autocrine/paracrine signals. We propose that endothelial cell migration relies on Cx43 hemichannel opening. Our findings reveal a novel mechanism of Ca2+ signaling and suggest that Cx43 hemichannels are key players in endothelial cell migration, providing potential therapeutic targets for deregulated angiogenesis in pathological conditions like cancer.