Azfar Mujahid, van Veen Sarah, Houdou Marine, Hamouda Norin Nabil, Eggermont Jan, Vangheluwe Peter
Laboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine, KU Leuven, B-3000 Leuven, Belgium; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, KU Leuven, B-3000 Leuven, Belgium.
Laboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine, KU Leuven, B-3000 Leuven, Belgium.
Biochim Biophys Acta Mol Cell Res. 2022 Dec;1869(12):119354. doi: 10.1016/j.bbamcr.2022.119354. Epub 2022 Sep 2.
Polyamines (PAs) are physiologically relevant molecules that are ubiquitous in all organisms. The vitality of PAs to the healthy functioning of a cell is due to their polycationic nature causing them to interact with a vast plethora of cellular players and partake in numerous cellular pathways. Naturally, the homeostasis of such essential molecules is tightly regulated in a strictly controlled interplay between intracellular synthesis and degradation, uptake from and secretion to the extracellular compartment, as well as intracellular trafficking. Not surprisingly, dysregulated PA homeostasis and signaling are implicated in multiple disorders, ranging from cancer to neurodegeneration; leading many to propose rectifying the PA balance as a potential therapeutic strategy. Despite being well characterized in bacteria, fungi and plants, the molecular identity and properties of the PA transporters in animals are poorly understood. This review brings together the current knowledge of the cellular function of the mammalian PA transport system (PTS). We will focus on the role of P5B-ATPases ATP13A2-5 which are PA transporters in the endosomal system that have emerged as key players in cellular PA uptake and organelle homeostasis. We will discuss recent breakthroughs on their biochemical and structural properties as well as their implications for disease and therapy.
多胺（PAs）是在所有生物体中普遍存在的具有生理相关性的分子。多胺对于细胞健康功能的重要性源于其多阳离子性质，这使得它们能够与大量细胞成分相互作用，并参与众多细胞途径。自然而然地，这类必需分子的体内平衡在细胞内合成与降解、细胞内外的摄取与分泌以及细胞内运输之间严格控制的相互作用中受到紧密调节。毫不奇怪，多胺体内平衡和信号传导失调与多种疾病有关，从癌症到神经退行性疾病不等；这使得许多人提出纠正多胺平衡作为一种潜在的治疗策略。尽管在细菌、真菌和植物中已得到充分表征，但动物体内多胺转运体的分子特性和性质仍知之甚少。本综述汇集了目前关于哺乳动物多胺转运系统（PTS）细胞功能的知识。我们将重点关注P5B - ATP酶ATP13A2 - 5的作用，它们是内体系统中的多胺转运体，已成为细胞摄取多胺和细胞器体内平衡的关键参与者。我们将讨论它们在生化和结构特性方面的最新突破以及它们对疾病和治疗的影响。
