Endocytosis of CF in marginal cells of stria vascularis regulated by ROCK and MLCK signaling cascade, but not G-proteins
Endocytosis of CF in marginal cells of stria vascularis regulated by ROCK and MLCK signaling cascade, but not G-proteins
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血管纹边缘细胞 CF 的内吞作用受 ROCK 和 MLCK 信号级联调节，但不受 G 蛋白调节
DOI：
10.1016/j.anl.2019.01.007
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发表时间：
2019
影响因子：
1.7
通讯作者：
Nibu Ken-ichi
中科院分区：
文献类型：
--
作者：
Kakigi Akinobu;Okada Teruhiko;Takeda Taizo;Uehara Natsumi;Nibu Ken-ichi
目的阳离子化的铁蛋白（CF）通过网格蛋白介导的内吞途径被一个信号网络调控。边缘细胞显示CF通过网格蛋白介导的途径进行主动内吞。通过这种网格蛋白介导的途径，受体的内化是信号转导中的重要调节事件。许多激酶参与内吞作用，并且每种内吞途径都受到细胞信号传导机制的高阶调节。方法将百日咳毒素（PTX）、肉毒梭菌C3毒素（BTX）、三磷酸鸟苷（GTP-γS）、ML-7、Y-27632分别注入耳蜗导管内，观察CF对耳蜗血管纹边缘细胞内吞的影响。结果在边缘细胞中，CF通过网格蛋白介导的依赖于F-肌动蛋白和微管（MT）的途径被内化。结论微过氧化物酶（MPO）的主要内吞途径不依赖于Rho/ROCK分子开关或肌动蛋白/肌球蛋白运动系统，而主要受RhoA信号级联的调控。目前的研究结果表明，这些信号级联调节CF内化完全不同于MPO内化的级联。
Objective The endocytosis of cationized feritin (CF) via a clathrin-mediated pathway is regulated by a signaling network. Marginal cells showed the active endocytosis of CF via a clathrin-mediated pathway. The internalization of receptors through this clathrin-mediated pathway is an important regulatory event in signal transduction. Numerous kinases are involved in endocytosis, and each endocytic route is subjected to high-order regulation by cellular signaling mechanisms. In this study, we investigated whether ROCK and MLCK signaling cascades and G-proteins regulate the endocytosis of CF in marginal cells of the stria vascularis.Methods CF was infused into the cochlear duct with pertussis toxin (PTX),Clostridium botulinum C3 toxin (BTX), guanosine(g-thio)-triphosphate (GTP-γS), ML-7, Y-27632. Endocytic activity was measured at 30 min after the start of infusion under an electron microscope.Results In marginal cells, CF was internalized via a clathrin-mediated pathway that depends on F-actin and microtubules (MT). Its processes were controlled by myosin light chain kinase (MLCK) and Rho-associated kinase (ROCK), but not affected by G-protein-coupled receptor (GPCR) or the RhoA signaling cascade.Conclusion Our previous study showed that the main endocytotic pathway of microperoxidase (MPO) did not depend on the Rho/ROCK molecular switch or actin/myosin motor system, but was mainly regulated by the RhoA signaling cascade. The present study results indicate that these signaling cascades regulating CF internalization completely differ from the cascades for MPO internalization.