MgcRacGAP restricts active RhoA at the cytokinetic furrow and both RhoA and Rac1 at cell-cell junctions in epithelial cells.
MgcRacGAP restricts active RhoA at the cytokinetic furrow and both RhoA and Rac1 at cell-cell junctions in epithelial cells.
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DOI：
10.1091/mbc.e14-11-1553
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发表时间：
2015-07-01
影响因子：
3.3
通讯作者：
Miller AL
中科院分区：
文献类型：
--
作者：
Breznau EB;Semack AC;Higashi T;Miller AL
研究了MgcRacGAP在调节上皮细胞中活性RhoA和Rac 1的时空动态中的作用。MgcRacGAP的GAP活性下调在沟处的RhoA以及在分裂的上皮细胞中的细胞-细胞连接处的RhoA和Rac 1，并且是成功的胞质分裂和细胞-细胞连接结构所需的。MgcRacGAP调节粘附连接的能力依赖于GAP活性和经由RhoA途径的信号传导。Rho GTP酶的局部激活对于多种细胞功能是必需的，包括胞质分裂以及细胞-细胞连接的形成和维持。虽然MgcRacGAP（Mgc）是必要的空间限制RhoA-GTP在赤道皮层的分裂细胞，Mgc的GAP活性的目标特异性和参与磷酸化的Mgc在Ser-386是有争议的。此外，Mgc在细胞-细胞连接处的功能仍不清楚。在这里，使用原肠胚阶段非洲爪蟾胚胎作为一个模型系统，我们研究MgC的作用，在调节本地化的RhoA-GTP和Rac 1-GTP在完整的脊椎动物上皮。我们发现，镁的GAP活性空间限制积累的RhoA-GTP和Rac 1-GTP在上皮细胞-RhoA在卵裂沟和RhoA和Rac 1在细胞-细胞连接处。Ser-386的磷酸化不会改变Mgc GAP活性的特异性，也不是成功的胞质分裂所必需的。此外，Mgc调节粘附连接但不调节紧密连接结构，并且调节粘附连接的能力依赖于GAP活性和经由RhoA途径的信号传导。总之，这些结果表明，Mgc的GAP活性下调活性群体的RhoA和Rac 1在局部区域的上皮细胞，是必要的成功的胞质分裂和细胞-细胞连接结构。
MgcRacGAP's role in regulating the spatiotemporal dynamics of active RhoA and Rac1 in epithelial cells is investigated. MgcRacGAP's GAP activity down-regulates RhoA at the furrow and both RhoA and Rac1 at cell–cell junctions in dividing epithelial cells and is required for successful cytokinesis and cell–cell junction structure. MgcRacGAP's ability to regulate adherens junctions is dependent on GAP activity and signaling via the RhoA pathway. Localized activation of Rho GTPases is essential for multiple cellular functions, including cytokinesis and formation and maintenance of cell–cell junctions. Although MgcRacGAP (Mgc) is required for spatially confined RhoA-GTP at the equatorial cortex of dividing cells, both the target specificity of Mgc's GAP activity and the involvement of phosphorylation of Mgc at Ser-386 are controversial. In addition, Mgc's function at cell–cell junctions remains unclear. Here, using gastrula-stage Xenopus laevis embryos as a model system, we examine Mgc's role in regulating localized RhoA-GTP and Rac1-GTP in the intact vertebrate epithelium. We show that Mgc's GAP activity spatially restricts accumulation of both RhoA-GTP and Rac1-GTP in epithelial cells—RhoA at the cleavage furrow and RhoA and Rac1 at cell–cell junctions. Phosphorylation at Ser-386 does not switch the specificity of Mgc's GAP activity and is not required for successful cytokinesis. Furthermore, Mgc regulates adherens junction but not tight junction structure, and the ability to regulate adherens junctions is dependent on GAP activity and signaling via the RhoA pathway. Together these results indicate that Mgc's GAP activity down-regulates the active populations of RhoA and Rac1 at localized regions of epithelial cells and is necessary for successful cytokinesis and cell–cell junction structure.