Cx43-formed hemichannels的开放介导了与内皮细胞迁移相关的Ca2+信号传导。
Opening of Cx43-formed hemichannels mediates the Ca2+ signaling associated with endothelial cell migration.
发表日期:2023 Aug 28
作者:
Hilda Espinoza, Xavier F Figueroa
来源:
Biology direct
摘要:
内皮细胞迁移是血管生成过程中的关键步骤。内皮细胞迁移的进展是通过在洞窟微领域中有序产生Ca2+信号的机制来协调的。连接蛋白(Cx)通过细胞间隙通过与细胞间连接的方式直接参与协调内皮细胞功能,并通过Cx形成的半通道间接地释放自分泌/旁分泌信号。然而,Cx半通道也对Ca2+有渗透性,并且Cx43可以与洞窟蛋白1(caveolin-1)结合,它是洞窟小室的结构蛋白。我们提出内皮细胞迁移依赖于Cx43半通道的开放。在这里,我们展示了内皮细胞迁移中的一种新的Ca2+信号机制。介导内皮细胞迁移和随后的管状结构形成的Ca2+信号依赖于Cx43半通道的开放,并且与Cx43与洞窟小室转位到细胞的后部相关。这些发现表明Cx43半通道在内皮细胞迁移中发挥着核心作用,并为治疗异常血管生成等病理情况提供了新的治疗靶点。 © 2023. BioMed Central Ltd.,身为Springer Nature的一部分。
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.© 2023. BioMed Central Ltd., part of Springer Nature.