Lauwers et al. have discovered how certain yeast membrane proteins end up in a cellular trash can.
The vacuole of yeast, like the lysosome of mammalian cells, is a disposal system for unwanted cellular components. According to Lauwers et al., two yeast proteins—one a disposer that resides in the vacuole, the other a disposee—are routed to this destructive organelle after being tagged with a special chain of ubiquitin molecules.
The addition of ubiquitin molecules—ubiquitylation—controls the function and cellular localization of a wide variety of proteins. This diversity seems to depend on the many different forms that ubiquitylation can take. For example, addition of a string of ubiquitins called a K48-linked chain is well known for sending proteins to another type of cellular trash can called the proteasome.
Lauwers et al. showed that addition of a single ubiquitin molecule to a plasma membrane protein called Gap1 permease prompted the protein's endocytosis. Addition of a K63-linked chain of ubiquitins, however, sent Gap1 to its destruction in the vacuole—via intermediate membrane compartments called multivesicular bodies (MVBs). K63-linked ubiquitylation also prompted MVB sorting of a second protein, carboxypeptidase S, to the vacuolar lumen—this particular protein's workplace.
K63-linked modification has been reported for a number of mammalian proteins destined for the lysosome, indicating that this signal and the pathway that recognizes it are conserved.