Abstract：
Plakophilin 4 (PKP4) is a component of cell-cell junctions that regulates intercellular adhesion and Rho-signaling during cytokinesis with an unknown function during epidermal differentiation. Here we show that keratinocytes lacking PKP4 fail to develop a cortical actin ring, preventing adherens junction maturation and generation of tissue tension. Instead, PKP4-depleted cells display increased stress fibers. PKP4-dependent RhoA localization at AJs was required to activate a RhoA-ROCK2-MLCK-MLC2 axis and organize actin into a cortical ring. AJ-associated PKP4 provided a scaffold for the Rho activator ARHGEF2 and the RhoA effectors MLCK and MLC2, facilitating the spatio-temporal activation of RhoA signaling at cell junctions to allow cortical ring formation and actomyosin contraction. In contrast, association of PKP4 with the Rho suppressor ARHGAP23 reduced ARHGAP23 binding to RhoA which prevented RhoA activation in the cytoplasm and stress fiber formation. These data identify PKP4 as an AJ component that transduces mechanical signals into cytoskeletal organization.
摘要：
Plakophilin4（PKP4）是细胞-细胞连接的组成部分，在表皮分化过程中具有未知的功能，在胞质分裂过程中调节细胞间粘附和Rho信号传导。在这里，我们发现缺乏PKP4的角质形成细胞无法形成皮质肌动蛋白环，防止粘附连接成熟和组织张力的产生。相反，PKP4耗尽的细胞显示出增加的应力纤维。需要PKP4依赖性RhoA在AJ上的定位来激活RhoA-ROCK2-MLCK-MLC2轴并将肌动蛋白组织成皮质环。AJ相关的PKP4为Rho激活剂ARHGEF2和RhoA效应子MLCK和MLC2提供了支架，促进了细胞连接处RhoA信号的时空激活，以允许皮质环形成和肌动球蛋白收缩。相比之下,PKP4与Rho抑制因子ARHGAP23的结合减少了ARHGAP23与RhoA的结合，从而阻止了细胞质中RhoA的激活和应激纤维的形成。这些数据将PKP4鉴定为将机械信号转导到细胞骨架组织中的AJ组分。
