ARHGEF18/p114RhoGEF Coordinates PKA/CREB Signaling and Actomyosin Remodeling to Promote Trophoblast Cell-Cell Fusion During Placenta Morphogenesis.
ARHGEF18/p114RhoGEF Coordinates PKA/CREB Signaling and Actomyosin Remodeling to Promote Trophoblast Cell-Cell Fusion During Placenta Morphogenesis.
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DOI：
10.3389/fcell.2021.658006
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发表时间：
2021
影响因子：
5.5
通讯作者：
Balda MS
中科院分区：
文献类型：
--
作者：
Beal R;Alonso-Carriazo Fernandez A;Grammatopoulos DK;Matter K;Balda MS
细胞-细胞粘附、肌动球蛋白动力学和基因表达的协调对于组织和器官发育的形态发生过程至关重要。Rho GTP酶是细胞骨架和粘附的主要调节剂。它们被鸟嘌呤核苷酸交换因子以空间和时间控制的方式激活。然而，在复杂的发育过程中，这些Rho GT3激活剂的作用仍然知之甚少。ARHGEF 18/p114 RhoGEF是一种紧密连接相关的RhoA激活剂，与肌球蛋白II形成复合物，并调节肌动球蛋白收缩性。在这里，我们表明，p114 RhoGEF/ARHGEF 18是必需的小鼠合体滋养层分化和胎盘发育。体外和体内实验证实p114 RhoGEF控制AKAP 12的表达，AKAP 12是一种调节蛋白激酶A（PKA）信号传导的蛋白，并且是PKA诱导的肌动球蛋白重塑、cAMP反应元件结合蛋白（CREB）驱动的滋养层分化所需蛋白的基因表达以及滋养层细胞-细胞融合所需的蛋白。因此，我们的数据表明，p114 RhoGEF链接肌动球蛋白动力学和细胞-细胞连接PKA/CREB信号，基因表达和细胞-细胞融合。
Coordination of cell-cell adhesion, actomyosin dynamics and gene expression is crucial for morphogenetic processes underlying tissue and organ development. Rho GTPases are main regulators of the cytoskeleton and adhesion. They are activated by guanine nucleotide exchange factors in a spatially and temporally controlled manner. However, the roles of these Rho GTPase activators during complex developmental processes are still poorly understood. ARHGEF18/p114RhoGEF is a tight junction-associated RhoA activator that forms complexes with myosin II, and regulates actomyosin contractility. Here we show that p114RhoGEF/ARHGEF18 is required for mouse syncytiotrophoblast differentiation and placenta development. In vitro and in vivo experiments identify that p114RhoGEF controls expression of AKAP12, a protein regulating protein kinase A (PKA) signaling, and is required for PKA-induced actomyosin remodeling, cAMP-responsive element binding protein (CREB)-driven gene expression of proteins required for trophoblast differentiation, and, hence, trophoblast cell-cell fusion. Our data thus indicate that p114RhoGEF links actomyosin dynamics and cell-cell junctions to PKA/CREB signaling, gene expression and cell-cell fusion.
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影响因子：
64.8
作者：
Perez-Garcia V;Fineberg E;Wilson R;Murray A;Mazzeo CI;Tudor C;Sienerth A;White JK;Tuck E;Ryder EJ;Gleeson D;Siragher E;Wardle-Jones H;Staudt N;Wali N;Collins J;Geyer S;Busch-Nentwich EM;Galli A;Smith JC;Robertson E;Adams DJ;Weninger WJ;Mohun T;Hemberger M
通讯作者：
Hemberger M
影响因子：
11.8
作者：
Acharya, Bipul R.;Nestor-Bergmann, Alexander;Yap, Alpha S.
通讯作者：
Yap, Alpha S.
影响因子：
4
作者：
Pidoux, Guillaume;Gerbaud, Pascale;Tasken, Kjetil
通讯作者：
Tasken, Kjetil
影响因子：
--
作者：
Li D;Sun Y;Kong X;Luan C;Yu Y;Chen F;Chen P
通讯作者：
Chen P
通过表达突变型紧密连接膜蛋白，细胞旁通透性和跨上皮电阻的功能性分离以及顶端-基底外侧膜内扩散屏障的破坏。
影响因子：
7.8
作者：
Balda, M S;Whitney, J A;Flores, C;Gonzalez, S;Cereijido, M;Matter, K
通讯作者：
Matter, K