The Motor Protein Myosin-X Transports VE-Cadherin along Filopodia To Allow the Formation of Early Endothelial Cell-Cell Contacts
The Motor Protein Myosin-X Transports VE-Cadherin along Filopodia To Allow the Formation of Early Endothelial Cell-Cell Contacts
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DOI：
10.1128/mcb.01226-09
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发表时间：
2010-04-01
影响因子：
5.3
通讯作者：
Gulino-Debrac, Danielle
中科院分区：
文献类型：
--
作者：
Almagro, Sebastien;Durmort, Claire;Gulino-Debrac, Danielle
血管内皮细胞（VE），即排列在血管树上的单层内皮细胞，在某些血管疾病的基础上受到损伤。其完整性由VE-钙粘蛋白维持，VE-钙粘蛋白是一种位于细胞-细胞连接处的粘附受体。在这里，我们表明，VE-钙粘蛋白也位于尖端和沿着丝状伪足稀疏或亚融合的内皮细胞。我们观察到VE-钙粘蛋白沿沿着丝状伪足内肌动蛋白丝航行。我们发现，肌动蛋白马达蛋白肌球蛋白-X是共定位的，并与丝状伪足VE-钙粘蛋白同步移动。免疫沉淀和下拉试验证实，肌球蛋白-X是直接与VE-钙粘蛋白复合物。此外，肌球蛋白-X的显性负突变体的表达揭示，肌球蛋白-X是需要VE-钙粘蛋白出口到细胞边缘和丝状伪足。这些特征表明肌球蛋白-X在肌动蛋白细胞骨架和VE-钙粘蛋白之间建立了联系，从而允许VE-钙粘蛋白沿沿着丝状伪足内肌动蛋白电缆运输。总之，我们提出VE-钙粘蛋白运输沿着丝状伪足使用肌球蛋白-X马达蛋白是细胞连接形成的先决条件。这种机制可能对病理环境中的内皮修复具有功能性后果。
Vascular endothelium (VE), the monolayer of endothelial cells that lines the vascular tree, undergoes damage at the basis of some vascular diseases. Its integrity is maintained by VE-cadherin, an adhesive receptor localized at cell-cell junctions. Here, we show that VE-cadherin is also located at the tip and along filopodia in sparse or subconfluent endothelial cells. We observed that VE-cadherin navigates along intrafilopodial actin filaments. We found that the actin motor protein myosin-X is colocalized and moves synchronously with filopodial VE-cadherin. Immunoprecipitation and pulldown assays confirmed that myosin-X is directly associated with the VE-cadherin complex. Furthermore, expression of a dominant-negative mutant of myosin-X revealed that myosin-X is required for VE-cadherin export to cell edges and filopodia. These features indicate that myosin-X establishes a link between the actin cytoskeleton and VE-cadherin, thereby allowing VE-cadherin transportation along intrafilopodial actin cables. In conclusion, we propose that VE-cadherin trafficking along filopodia using myosin-X motor protein is a prerequisite for cell-cell junction formation. This mechanism may have functional consequences for endothelium repair in pathological settings.