Smith Madeleine R, Costa Guilherme
Wellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast BT9 7BL, U.K.
Biochem Soc Trans. 2024 Dec 19;52(6):2569-2578. doi: 10.1042/BST20241021.
Regionalisation of molecular mechanisms allows cells to fine-tune their responses to dynamic environments. In this context, scaffolds are well-known mediators of localised protein activity. These phenomenal proteins act as docking sites where pathway components are brought together to ensure efficient and reliable flow of information within the cell. Although scaffolds are mostly understood as hubs for signalling communication, some have also been studied as regulators of mRNA translation. Here, we provide a brief overview of the work unravelling how scaffolding proteins facilitate the cross-talk between the two processes. Firstly, we examine the activity of AKAP1 and AKAP12, two signalling proteins that not only have the capacity to anchor mRNAs to membranes but can also regulate protein synthesis. Next, we review the studies that uncovered how the ribosome-associated protein RACK1 orchestrates translation initiation. We also discuss the evidence pointing to the scaffolds Ezrin and LASP1 as regulators of early translation stages. In the end, we conclude with some open questions and propose future directions that will bring new insights into the regulation of mRNA translation by scaffolding proteins.
分子机制的区域化使细胞能够对动态环境做出精确的反应。在这种情况下，支架蛋白是局部蛋白质活性的著名介质。这些非凡的蛋白质充当对接位点，信号通路的组分在这些位点聚集，以确保细胞内信息的高效可靠传递。虽然支架蛋白大多被认为是信号传导通讯的枢纽，但也有一些被研究作为mRNA翻译的调节因子。在这里，我们简要概述了揭示支架蛋白如何促进这两个过程之间相互作用的研究工作。首先，我们研究了AKAP1和AKAP12这两种信号蛋白的活性，它们不仅能够将mRNA锚定到膜上，还能调节蛋白质合成。接下来，我们回顾了揭示核糖体相关蛋白RACK1如何协调翻译起始的研究。我们还讨论了支持支架蛋白埃兹蛋白（Ezrin）和LASP1作为早期翻译阶段调节因子的证据。最后，我们以一些未解决的问题作为结论，并提出未来的研究方向，这些方向将为支架蛋白对mRNA翻译的调控带来新的见解。
