Addition of a K63-linked chain of ubiquitins drives Gap1 permease (green) to the vacuole (red) via MVBs in yeast cells.

Addition of a K63-linked chain of ubiquitins drives Gap1 permease (green) to the vacuole (red) via MVBs in yeast cells.

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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.

Lauwers
E.
et al
.
2009
.
J. Cell Biol.
doi: .