Ngo Jordan Matthew, Williams Justin Krish, Zhang Congyan, Saleh Amr Hosny, Liu Xiao-Man, Ma Liang, Schekman Randy
Department of Molecular and Cell Biology, University of California, Berkeley, California, USA; email:
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Annu Rev Biochem. 2025 Jun;94(1):587-609. doi: 10.1146/annurev-biochem-100924-012717. Epub 2025 Mar 18.
Extracellular vesicles (EVs) are secreted, membrane-enclosed particles that have been proposed to play a broad role in intercellular communication. Most often, EVs, by analogy to enveloped viruses, are suggested to fuse to or within a target cell to deliver a soluble signaling molecule into the cytoplasm. However, significant evidence supports an alternative model in which EVs are secreted to promote homeostasis. In this model, EVs are loaded with unwanted or toxic cargo, secreted upon cellular or organismal stress, and degraded by other cells. Here, we present evidence supporting this homeostatic EV model and discuss the general inefficiency of EV cargo delivery. While the homeostatic and viral delivery models for EV function are not mutually exclusive, we propose that much of the evidence presented is hard to reconcile with a broad role for EVs in cargo transfer as a means to promote intercellular communication.
细胞外囊泡(EVs)是分泌的、被膜包裹的颗粒,有人提出它们在细胞间通讯中发挥广泛作用。最常见的情况是,类似于包膜病毒,EVs被认为会与靶细胞融合或进入靶细胞内,将可溶性信号分子递送至细胞质中。然而,大量证据支持另一种模型,即EVs被分泌出来以促进内环境稳定。在这个模型中,EVs装载着不需要的或有毒的物质,在细胞或机体受到应激时被分泌出来,并被其他细胞降解。在这里,我们提供支持这种内环境稳定的EV模型的证据,并讨论EV货物递送的总体低效性。虽然EV功能的内环境稳定模型和病毒递送模型并非相互排斥,但我们认为,所呈现的许多证据很难与EVs在货物转运中作为促进细胞间通讯手段的广泛作用相协调。