Directionality is a challenge for vesicle traffic. Although vesicles traveling from ER to Golgi and from Golgi to ER have very different job descriptions, recycling of transport proteins ensures that the compositions of the two vesicle types are similar if not identical. The two vesicle types start off with different coats (COPII for ER to Golgi and COPI for Golgi to ER) but shed them soon after departure.
Kamena and Spang figured that vesicles departing from the ER might be prevented from doing a U-turn by the same ER machinery that welcomes fusion of Golgi-derived vesicles. Sure enough, a mutant of the ER protein Tip20p allowed COPII vesicles, recently departed from the ER, to fuse back to the ER.
The researchers were lucky that they tested two different Tip20p mutants. Only one of those mutants (tip20–8, and not tip20–5 or any of the other ER fusion mutants) showed the U-turn phenotype. Now, the team can look for suppressor mutations that rescue tip20–8 but not tip20–5, and isolate proteins that bind only one of the two mutant proteins. Either approach may give clues about what, exactly, is sensed as different about a departing versus an arriving vesicle. ▪