The inside of a cell is abuzz with activity… including constant shipments of proteins in membrane-bounded vesicles. Antibodies headed out to the bloodstream to fight disease; enzymes destined for lysosomes to break down and recycle cellular material . But how do all these vesicular parcels get to the right place? It’s already known that long proteins called golgins serve as addresses for and help capture vesicles heading to the Golgi apparatus, the cell’s central sorting station. But little is known about how they do it. Now, researchers at the MRC Laboratory of Molecular Biology in the UK have tracked down the parts of the golgins that act as postal codes.
To find out which parts of the golgins provide this critical address function, the team relocated the proteins to the mitochondria, then deleted or mutated different sections to see which sequences were critical for capturing vesicles. They tested six mammalian golgins, and found that bits located at the N-terminal ends were doing all the postal code work: when attached to other proteins, these sequences were sufficient for tethering.
Perhaps not surprisingly, the postal codes were generally well conserved across species. When the team examined the sequences in more detail, they found that the three golgins that capture vesicles traveling within the Golgi all shared a short N-terminal motif. Of the three golgins that grab cargo coming from endosomes, two had nearly identical postal code domains, but the third was very distinct.
The findings suggest that for most golgins, vesicle capture is handled almost exclusively by the N-terminus, although the precise mechanisms and types of vesicles are likely to vary. It’s still unclear why the golgins seem to bind only at the very end, placing vesicles the furthest from their fusion target, or what vesicular molecules the golgins bind to. Future work may answer these questions and reveal how eukaryotes evolved such a diverse postal code system for membrane trafficking.