p115RhoGEF activates RhoA to support tight junction maintenance and remodeling.
p115RhoGEF activates RhoA to support tight junction maintenance and remodeling.
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DOI：
10.1091/mbc.e22-06-0205
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发表时间：
2022-12-01
影响因子：
3.3
通讯作者：
Miller, Ann L.
中科院分区：
文献类型：
--
作者：
Chumki, Shahana A.;van den Goor, Lotte M.;Hall, Benjamin N.;Miller, Ann L.
在脊椎动物中，上皮细胞-细胞连接必须迅速重塑，以维持屏障功能，因为细胞经历动态形状变化事件。因此，局部泄漏有时会出现在紧密连接（TJ）屏障内，这是由RhoA的短暂激活修复的，称为“Rho耀斑”。然而，RhoA如何在泄漏部位被激活仍然未知。在这里，我们问的鸟嘌呤核苷酸交换因子（GEF）本地化的TJ启动Rho活动在Rho耀斑。我们发现，p115 RhoGEF局部激活Rho耀斑在网站的TJ损失。p115 RhoGEF的敲低导致Rho耀斑强度降低和TJ重塑受损。p115 RhoGEF敲除也降低了连接活性RhoA水平，从而损害了顶端肌动球蛋白阵列和连接复合体。此外，p115 RhoGEF是必要的，以促进局部泄漏修复，以维持TJ屏障功能。总之，我们的工作证明了p115 RhoGEF在激活连接RhoA以保持屏障功能和指导局部TJ重塑中的核心作用。
In vertebrates, epithelial cell–cell junctions must rapidly remodel to maintain barrier function as cells undergo dynamic shape-change events. Consequently, localized leaks sometimes arise within the tight junction (TJ) barrier, which are repaired by short-lived activations of RhoA, called “Rho flares.” However, how RhoA is activated at leak sites remains unknown. Here we asked which guanine nucleotide exchange factor (GEF) localizes to TJs to initiate Rho activity at Rho flares. We find that p115RhoGEF locally activates Rho flares at sites of TJ loss. Knockdown of p115RhoGEF leads to diminished Rho flare intensity and impaired TJ remodeling. p115RhoGEF knockdown also decreases junctional active RhoA levels, thus compromising the apical actomyosin array and junctional complex. Furthermore, p115RhoGEF is necessary to promote local leak repair to maintain TJ barrier function. In all, our work demonstrates a central role for p115RhoGEF in activating junctional RhoA to preserve barrier function and direct local TJ remodeling.
影响因子：
3.7
作者：
Kher SS;Struckhoff AP;Alberts AS;Worthylake RA
通讯作者：
Worthylake RA