Syndecan-4 phosphorylation is a control point for integrin recycling.
Syndecan-4 phosphorylation is a control point for integrin recycling.
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DOI：
10.1016/j.devcel.2013.01.027
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发表时间：
2013-03-11
影响因子：
11.8
通讯作者：
Humphries, Martin J.
中科院分区：
文献类型：
--
作者：
Morgan, Mark R.;Hamidi, Hellyeh;Bass, Mark D.;Warwood, Stacey;Ballestrem, Christoph;Humphries, Martin J.
整合素粘附复合物动力学的精确时空协调对于有效的细胞迁移是必不可少的。对于粘附于纤连蛋白的细胞，α5β1和αVβ3整合素的差异接合用于引起粘附复合物稳定性、机械感觉、基质组装和迁移的变化，但负责受体调节的机制在很大程度上仍然不清楚。我们确定磷酸化的膜插入蛋白聚糖syndecan-4作为一个重要的开关控制整合素回收。Src磷酸化syndecan-4，并通过驱动syntenin结合，导致抑制Arf 6活性和以α5β1为代价将αVβ3再循环至质膜。αVβ3接合的结果升高促进了局灶性粘连的稳定。相反，多配体蛋白聚糖-4磷酸化的消除驱动α5β1的表面表达，使粘附复合物不稳定，并破坏细胞迁移。这些数据确定了Src介导的syndecan-4磷酸化的动态时空调节作为控制整合素运输和粘附动力学的重要开关，以促进有效的细胞迁移。Syndecan-4磷酸化和接合调节Arf 6活性Syndecan-4介导的Arf 6活性调节差异整合素再循环Syndecan-4介导的整合素再循环控制FA动力学和细胞迁移有效的细胞迁移需要动态协调细胞-基质相互作用，部分通过精确的时空控制整合素粘附动力学。Morgan等人显示了细胞外基质受体多配体蛋白聚糖-4的磷酸化作为分子开关，在粘附动力学的控制中差异性地指导α5β1或αVβ3整联蛋白再循环。
Precise spatiotemporal coordination of integrin adhesion complex dynamics is essential for efficient cell migration. For cells adherent to fibronectin, differential engagement of α5β1 and αVβ3 integrins is used to elicit changes in adhesion complex stability, mechanosensation, matrix assembly, and migration, but the mechanisms responsible for receptor regulation have remained largely obscure. We identify phosphorylation of the membrane-intercalated proteoglycan syndecan-4 as an essential switch controlling integrin recycling. Src phosphorylates syndecan-4 and, by driving syntenin binding, leads to suppression of Arf6 activity and recycling of αVβ3 to the plasma membrane at the expense of α5β1. The resultant elevation in αVβ3 engagement promotes stabilization of focal adhesions. Conversely, abrogation of syndecan-4 phosphorylation drives surface expression of α5β1, destabilizes adhesion complexes, and disrupts cell migration. These data identify the dynamic spatiotemporal regulation of Src-mediated syndecan-4 phosphorylation as an essential switch controlling integrin trafficking and adhesion dynamics to promote efficient cell migration. ► c-Src phosphorylates syndecan-4 in response to extracellular stimuli ► Syndecan-4 phosphorylation and engagement regulate Arf6 activity ► Syndecan-4-mediated Arf6 activity regulates differential integrin recycling ► Syndecan-4-mediated integrin recycling controls FA dynamics and cell migration Efficient cell migration requires dynamic coordination of cell-matrix interactions, in part through precise spatiotemporal control of integrin adhesion dynamics. Morgan et al. show that phosphorylation of the extracellular matrix receptor syndecan-4 acts as a molecular switch, differentially directing either α5β1 or αVβ3 integrin recycling in the control of adhesion dynamics.
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影响因子：
3.4
作者：
Bass, Mark D.;Morgan, Mark R.;Humphries, Martin J.
通讯作者：
Humphries, Martin J.
影响因子：
56.9
作者：
Hu, Ke;Ji, Lin;Waterman-Storer, Clare M.
通讯作者：
Waterman-Storer, Clare M.
影响因子：
9.2
作者：
Dunphy, JL;Moravec, R;Casanova, JE
通讯作者：
Casanova, JE
影响因子：
4.8
作者：
ASUNDI, VK;CAREY, DJ
通讯作者：
CAREY, DJ
影响因子：
11.2
作者：
Muralidharan-Chari V;Hoover H;Clancy J;Schweitzer J;Suckow MA;Schroeder V;Castellino FJ;Schorey JS;D'Souza-Schorey C
通讯作者：
D'Souza-Schorey C