Rap1 potentiates endothelial cell junctions by spatially controlling myosin II activity and actin organization.
Rap1 potentiates endothelial cell junctions by spatially controlling myosin II activity and actin organization.
复制标题
DOI：
10.1083/jcb.201301115
复制
发表时间：
2013-09-16
期刊：
影响因子：
--
通讯作者：
Mochizuki N
中科院分区：
文献类型：
--
作者：
Ando K;Fukuhara S;Moriya T;Obara Y;Nakahata N;Mochizuki N
Rap 1通过激活Cdc 42-MRCK通路和抑制Rho-ROCK通路，在空间上控制非肌肉肌球蛋白II活性，从而增强内皮细胞连接。肌动蛋白细胞骨架的重组负责内皮细胞（EC）屏障功能的动态调节。周向肌动蛋白束（CAB）促进线性粘附连接（AJs）的形成和EC连接的收紧，而连接到点状AJs的径向应力纤维（RSF）的形成发生在连接重塑过程中。小的GTdR Rap 1诱导CAB的形成，以加强EC连接，然而，Rap 1诱导的CAB形成的机制仍然未知。在这里，我们表明，强直性肌营养不良激酶相关的CDC 42结合激酶（MRCK）介导的激活非肌肉肌球蛋白II（NM-II）在细胞-细胞接触是必不可少的Rap 1诱导的CAB形成。我们的数据表明，Rap 1诱导FGD 5依赖性Cdc 42在细胞-细胞连接处激活，通过MRCK局部激活NM-II，从而诱导CAB形成。我们进一步揭示，Rap 1抑制由Rho-ROCK途径刺激的NM-II活性，导致RSF溶解。这些发现意味着Rap 1通过激活Cdc 42-MRCK途径和抑制Rho-ROCK途径在空间上控制NM-II活性来增强EC连接。
Rap1 potentiates endothelial cell junctions by spatially controlling non-muscle myosin II activity through activation of the Cdc42–MRCK pathway and suppression of the Rho–ROCK pathway. Reorganization of the actin cytoskeleton is responsible for dynamic regulation of endothelial cell (EC) barrier function. Circumferential actin bundles (CAB) promote formation of linear adherens junctions (AJs) and tightening of EC junctions, whereas formation of radial stress fibers (RSF) connected to punctate AJs occurs during junction remodeling. The small GTPase Rap1 induces CAB formation to potentiate EC junctions; however, the mechanism underlying Rap1-induced CAB formation remains unknown. Here, we show that myotonic dystrophy kinase–related CDC42-binding kinase (MRCK)-mediated activation of non-muscle myosin II (NM-II) at cell–cell contacts is essential for Rap1-induced CAB formation. Our data suggest that Rap1 induces FGD5-dependent Cdc42 activation at cell–cell junctions to locally activate the NM-II through MRCK, thereby inducing CAB formation. We further reveal that Rap1 suppresses the NM-II activity stimulated by the Rho–ROCK pathway, leading to dissolution of RSF. These findings imply that Rap1 potentiates EC junctions by spatially controlling NM-II activity through activation of the Cdc42–MRCK pathway and suppression of the Rho–ROCK pathway.
登录
查看更多内容
影响因子：
4
作者：
Dejana, Elisabetta;Orsenigo, Fabrizio;Lampugnani, Maria Grazia
通讯作者：
Lampugnani, Maria Grazia
影响因子：
9.2
作者：
Abraham, Sabu;Yeo, Margaret;Mavria, Georgia
通讯作者：
Mavria, Georgia
影响因子：
5.3
作者：
Fukuhara, S;Sakurai, A;Mochizuki, N
通讯作者：
Mochizuki, N
影响因子：
4.8
作者：
Borikova, Asya L.;Dibble, Christopher F.;Johnson, Gary L.
通讯作者：
Johnson, Gary L.
DOI：
10.1161/atvbaha.111.244004
发表时间：
2012-04-01
影响因子：
8.7
作者：
Kurogane, Yusuke;Miyata, Muneaki;Rikitake, Yoshiyuki
通讯作者：
Rikitake, Yoshiyuki