Exosome secretion and a tethering protein: Does tetherin tether?

Exosomes are small membrane vesicles that play an important role in communication between cells. This process is natural, however, its upregulation is associated with certain diseases, such as cancer. Exosomes start their journey from the cell in larger vesicles known as multivesicular bodies (MVBs). When exosomes are secreted, the MVBs fuse with the cellular membrane, and the exosomes inside them move away from the fusion site. Observations of this process show that the exosomes take a much longer time to leave the fusion site than they would if they were moving freely. This suggests that there is something hindering the movement of the exosomes after they are secreted. We have developed a simulation of this process in MATLAB allowing us to accurately replicate experimental observations of the kinetics of this process. Based on the results of the simulation, two mechanisms for the tethering were proposed. Additionally, experimental work utilizing the protein tetherin was performed to find out whether the protein plays a role in the hindrance of the movement of exosomes. FRAP showed an agreement between the diffusion coefficient of tetherin inside the cellular membrane and simulation. Western blot was used to quantify the expression of tetherin during these experiments. These experiments yielded some data suggesting that tetherin plays a role in the process, however, the results are not conclusive yet. Future work will involve studying the relationship between tetherin expression and the amount of exosomes secreted by the cells, which could provide conclusive evidence about the involvement of tetherin in the process.