Randy Schekman, University of California, Berkeley and Lelio Orci, University of Geneva Switzerland
C. Lord et al., “Sequential interactions with Sec23 control the direction of vesicle traffic,” Nature, 473:181-86, 2011. Free 1000 Evaluation.
Transport vesicles deliver cargo to various targets inside the cell, “but if the vesicle goes to the wrong place,” says Susan Ferro-Novick, at the University of California, San Diego, “you have a mess on your hands.” She and her colleagues discovered that a coat of vesicle proteins called COPII, which is responsible for choosing what goes into each vesicle, also serves as the address label that gets the vesicle to the right place in the cell.
The promiscuity problem
Many researchers believed that SNARE proteins, which help vesicles dock to target membranes, acted as address labels. The problem is that SNAREs aren’t very picky about which other SNAREs they bind. Without this specificity, vesicles that bud off the ER might “simply fuse directly back with their donor compartment,” says Elizabeth Miller of Columbia University.
The researchers used yeast mutants or blocking antibodies to cripple different steps in vesicle targeting and fusion and then measured vesicle traffic between the ER and the Golgi. They found that under normal circumstances, COPII coat proteins are not shed immediately after budding, as many researchers thought. Instead, they remain in place long enough for the vesicle to be recognized by the target.
The chain of events
Ferro-Novick thinks that as soon as the COPII coat protein address label is recognized by a long tethering protein that pulls the vesicle to its target, the coat proteins are shed and fusion occurs.