Identification of lysophosphatidic acid in serum as a factor that promotes epithelial apical junctional complex organization.
Identification of lysophosphatidic acid in serum as a factor that promotes epithelial apical junctional complex organization.
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鉴定血清中溶血磷酸酸是促进上皮顶连接复合物组织的因素。
DOI：
10.1016/j.jbc.2022.102426
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发表时间：
2022-10
影响因子：
4.8
通讯作者：
Takai, Yoshimi
中科院分区：
文献类型：
--
作者：
Sakakibara, Shotaro;Sakane, Ayuko;Sasaki, Takuya;Shinohara, Masakazu;Maruo, Tomohiko;Miyata, Muneaki;Mizutani, Kiyohito;Takai, Yoshimi
顶端连接复合体 (AJC) 由粘附连接 (AJ) 和紧密连接组成，调节上皮完整性和重塑。然而，目前尚不清楚 AJC 组织如何根据环境线索进行监管。我们使用培养的 EpH4 小鼠乳腺上皮细胞发现，培养基中的胎牛血清 (FBS) 显示出促进 AJC 组织的活性，并且即使在没有 AJ 蛋白（例如 E-钙粘蛋白、αE-连环蛋白和阿法丁）的情况下，FBS 也显示出促进紧密连接形成的活性。此外，我们从胎牛血清中纯化了负责这些功能的单个因子，并将该分子鉴定为溶血磷脂酸（LPA）。在验证实验中，纯化的 LPA 引发了与 FBS 相同的活性。此外，我们发现 LPA 的 AJC 组织促进活性是通过 LPA 受体 1/5 通过二酰基甘油-新型 PKC 和 Rho-ROCK 通路激活以相互独立但互补的方式介导的。我们证明，Rho-ROCK 通路激活介导的 AJC 组织独立于肌球蛋白 II 诱导的肌动球蛋白收缩，尽管之前已证明该信号通路可诱导肌球蛋白 II 激活。这些发现与文献相反，因为之前的结果表明 AJC 组织扰乱了 LPA 的活动。目前的结果表明，血清中的 LPA 具有 AJC 组织促进活性，其方式依赖于或独立于 AJ 蛋白。
The apical junctional complex (AJC) consists of adherens junctions (AJs) and tight junctions and regulates epithelial integrity and remodeling. However, it is unclear how AJC organization is regulated based on environmental cues. We found here using cultured EpH4 mouse mammary epithelial cells that fetal bovine serum (FBS) in a culture medium showed an activity to promote AJC organization and that FBS showed an activity to promote tight junction formation even in the absence of AJ proteins, such as E-cadherin, αE-catenin, and afadin. Furthermore, we purified the individual factor responsible for these functions from FBS and identified this molecule as lysophosphatidic acid (LPA). In validation experiments, purified LPA elicited the same activity as FBS. In addition, we found that the AJC organization–promoting activity of LPA was mediated through the LPA receptor 1/5 via diacylglycerol–novel PKC and Rho–ROCK pathway activation in a mutually independent, but complementary, manner. We demonstrated that the Rho–ROCK pathway activation–mediated AJC organization was independent of myosin II-induced actomyosin contraction, although this signaling pathway was previously shown to induce myosin II activation. These findings are in contrast to the literature, as previous results suggested an AJC organization–disrupting activity of LPA. The present results indicate that LPA in serum has an AJC organization–promoting activity in a manner dependent on or independent of AJ proteins.
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影响因子：
8
作者：
Fukuhara, A;Irie, K;Takai, Y
通讯作者：
Takai, Y
影响因子：
7.2
作者：
Cavey, Matthieu;Lecuit, Thomas
通讯作者：
Lecuit, Thomas
单个基因产物Claudin -1或-2，在成纤维细胞中重构紧密结合的连接链和新兵。
影响因子：
7.8
作者：
Furuse, M;Sasaki, H;Fujimoto, K;Tsukita, S
通讯作者：
Tsukita, S
DOI：
10.1083/jcb.107.4.1575
发表时间：
1988-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gumbiner B;Stevenson B;Grimaldi A
通讯作者：
Grimaldi A
影响因子：
21.3
作者：
Bertocchi C;Wang Y;Ravasio A;Hara Y;Wu Y;Sailov T;Baird MA;Davidson MW;Zaidel-Bar R;Toyama Y;Ladoux B;Mege RM;Kanchanawong P
通讯作者：
Kanchanawong P