Unpacking the Cell’s UPS: The role of vesicle tethers in cell membrane fusion

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Vesicular transport is a vital process that allows proteins to travel from one location to another in package-like vesicles. When a vesicle reaches its target membrane, it has two fates. It can undergo full fusion, in which the vesicle completely fuses with the membrane to deliver its cargo. Alternatively, it can undergo kiss-and-run, in which the vesicle connects with the membrane before rapidly reclosing. Seong An, a research associate at the Yale School of Medicine, discovered that bridge-like vesicle tethers, such as exocyst complexes, play an unexpected role in fusion mode selectivity. 

To investigate the exocyst’s role in the tethering process, An first mutated Exo70, an exocyst subunit, so that it could no longer directly bind to the membrane. Unexpectedly, this did not prevent tethering—instead, it promoted kiss-and-run over full fusion. When membrane binding by the mutated Exo70 was “rescued” using optogenetics, a technique that uses light to control protein function, full fusion occurred. Finally, An found that in the absence of the exocyst, vesicles that were optogenetically tethered to the membrane merely underwent kiss-and-stay, a version of kiss-and-run in which the vesicle remains at the membrane after fusing. “The evidence suggests that membrane binding by Exo70 is not necessary for tethering but vital for the mode of vesicle fusion,” An said.

Further research may shed light on cellular processes such as cell migration, as full fusion events play a role in membrane expansion. “Now that we’re able to observe vesicle tethering in real time, we can study what kind of impact membrane fusion has physiologically,” An said.