Intermedin promotes vessel fusion by inducing VE-cadherin accumulation at potential fusion sites and to achieve a dynamic balance between VE-cadherin-complex dissociation/reconstitution.
Intermedin promotes vessel fusion by inducing VE-cadherin accumulation at potential fusion sites and to achieve a dynamic balance between VE-cadherin-complex dissociation/reconstitution.
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Intermedin 通过诱导 VE-钙粘蛋白在潜在融合位点积累来促进血管融合，并实现 VE-钙粘蛋白-复合物解离/重建之间的动态平衡
作者：
Kong L;Xiao F;Wang L;Li M;Wang D;Feng Z;Huang L;Wei Y;Li H;Liu F;Kang Y;Liao X;Zhang W
摘要为了建立一个封闭的血管系统，血管新生芽必须在一个称为血管融合的过程中相遇和连接，这是在新生血管中建立适当血流的先决条件。然而，这一过程背后的分子机制在很大程度上仍然未知。在此，我们报道了降钙素家族成员中介素（IMD）通过诱导内皮细胞（EC）进入“准备锚”状态来促进血管融合。IMD促进血管内皮钙粘蛋白（VEC）在潜在融合部位的积聚，以促进接近血管相互锚定。同时，IMD微调VEC活性，以实现VEC复合体解离和重建之间的动态平衡，从而扩大吻合点。IMD诱导持续的VEC磷酸化。内化的磷酸化VEC优先与Rab 4和Rab 11结合，这有助于VEC囊泡再循环回到细胞-细胞接触，以重建VEC复合物。这种新的机制可以解释新生血管如何接触和融合到相邻的血管，创造一个封闭的血管系统。
Abstract To create a closed vascular system, angiogenic sprouts must meet and connect in a process called vessel fusion, which is a prerequisite for establishment of proper blood flow in nascent vessels. However, the molecular machinery underlying this process remains largely unknown. Herein, we report that intermedin (IMD), a calcitonin family member, promotes vessel fusion by inducing endothelial cells (ECs) to enter a “ready‐to‐anchor” state. IMD promotes vascular endothelial cadherin (VEC) accumulation at the potential fusion site to facilitate anchoring of approaching vessels to each other. Simultaneously, IMD fine‐tunes VEC activity to achieve a dynamic balance between VEC complex dissociation and reconstitution in order to widen the anastomotic point. IMD induces persistent VEC phosphorylation. Internalized phospho‐VEC preferentially binds to Rab4 and Rab11, which facilitate VEC vesicle recycling back to the cell‐cell contact for reconstruction of the VEC complex. This novel mechanism may explain how neovessels contact and fuse to adjacent vessels to create a closed vascular system.
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影响因子：
2.7
作者：
Blum, Yannick;Belting, Heinz-Georg;Affolter, Markus
通讯作者：
Affolter, Markus
影响因子：
7.5
作者：
Harris ES;Nelson WJ
通讯作者：
Nelson WJ
DOI：
10.1038/nrm3176
发表时间：
2011-08-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
9.2
作者：
Herwig, Lukas;Blum, Yannick;Affolter, Markus
通讯作者：
Affolter, Markus
影响因子：
20.3
作者：
Fantin, Alessandro;Vieira, Joaquim M.;Ruhrberg, Christiana
通讯作者：
Ruhrberg, Christiana