Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, Chatham ME4 4ZF, UK.
Int J Mol Sci. 2022 Apr 23;23(9):4684. doi: 10.3390/ijms23094684.
Cellular trafficking through the endosomal-lysosomal system is essential for the transport of cargo proteins, receptors and lipids from the plasma membrane inside the cells and across membranous organelles. By acting as sorting stations, vesicle compartments direct the fate of their content for degradation, recycling to the membrane or transport to the trans-Golgi network. To effectively communicate with their neighbors, cells need to regulate their compartmentation and guide their signaling machineries to cortical membranes underlying these contact sites. Endosomal trafficking is indispensable for the polarized distribution of fate determinants, adaptors and junctional proteins. Conversely, endocytic machineries cooperate with polarity and scaffolding components to internalize receptors and target them to discrete membrane domains. Depending on the cell and tissue context, receptor endocytosis can terminate signaling responses but can also activate them within endosomes that act as signaling platforms. Therefore, cell homeostasis and responses to environmental cues rely on the dynamic cooperation of endosomal-lysosomal machineries with polarity and signaling cues. This review aims to address advances and emerging concepts on the cooperative regulation of endocytosis, polarity and signaling, primarily in and discuss some of the open questions across the different cell and tissue types that have not yet been fully explored.
细胞内吞通过内体-溶酶体系统对于将货物蛋白、受体和脂质从细胞质膜运输到细胞内和跨膜细胞器是必不可少的。通过充当分拣站，囊泡隔室可以决定其内容物的命运，是进行降解、回收再利用到膜上还是运输到反式高尔基体网络。为了有效地与它们的邻居进行交流，细胞需要调节它们的区室化，并引导它们的信号机制到这些接触位点下的皮质膜上。内体运输对于命运决定因素、衔接蛋白和连接蛋白的极化分布是不可或缺的。相反，内吞机制与极性和支架成分合作，将受体内化并将其靶向到离散的膜域。根据细胞和组织的背景，受体内吞可以终止信号反应，但也可以在作为信号平台的内体中激活它们。因此，细胞的动态平衡和对环境信号的反应依赖于内体-溶酶体机制与极性和信号的动态合作。这篇综述旨在讨论内吞、极性和信号之间的合作调控方面的进展和新兴概念，主要在 和 中讨论，并讨论一些尚未得到充分探索的不同细胞和组织类型的开放性问题。
