Pedrioli Giona, Paganetti Paolo
Neurodegeneration Research Group, Laboratory for Biomedical Neurosciences, Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Torricella-Taverne, Switzerland.
Member of the International Ph.D. Program of the Biozentrum, University of Basel, Basel, Switzerland.
Front Cell Dev Biol. 2021 Jan 7;8:595515. doi: 10.3389/fcell.2020.595515. eCollection 2020.
Extracellular vesicles, phospholipid bilayer-membrane vesicles of cellular origin, are emerging as nanocarriers of biological information between cells. Extracellular vesicles transport virtually all biologically active macromolecules (e.g., nucleotides, lipids, and proteins), thus eliciting phenotypic changes in recipient cells. However, we only partially understand the cellular mechanisms driving the encounter of a soluble ligand transported in the lumen of extracellular vesicles with its cytosolic receptor: a step required to evoke a biologically relevant response. In this context, we review herein current evidence supporting the role of two well-described cellular transport pathways: the endocytic pathway as the main entry route for extracellular vesicles and the autophagic pathway driving lysosomal degradation of cytosolic proteins. The interplay between these pathways may result in the target engagement between an extracellular vesicle cargo protein and its cytosolic target within the acidic compartments of the cell. This mechanism of cell-to-cell communication may well own possible implications in the pathogenesis of neurodegenerative disorders.
细胞外囊泡是细胞来源的磷脂双分子层膜囊泡，正逐渐成为细胞间生物信息的纳米载体。细胞外囊泡几乎能运输所有具有生物活性的大分子（如核苷酸、脂质和蛋白质），从而引起受体细胞的表型变化。然而，我们对驱动细胞外囊泡腔内运输的可溶性配体与其胞质受体相遇的细胞机制仅了解一部分：这是引发生物学相关反应所需的一个步骤。在此背景下，我们在此回顾支持两种已充分描述的细胞运输途径作用目前的证据：内吞途径作为细胞外囊泡的主要进入途径，以及自噬途径驱动胞质蛋白的溶酶体降解。这些途径之间的相互作用可能导致细胞外囊泡货物蛋白与其细胞内酸性区室中的胞质靶标之间的靶标结合。这种细胞间通讯机制很可能在神经退行性疾病的发病机制中具有潜在意义。
