A new class of lysosomal/vacuolar protein sorting signals.

A number of inherited lysosomal diseases are known to result from missorting of lysosomal proteins. Considerable attention has been directed toward an understanding of this sorting pathway, and it has become apparent that different mechanisms are used for the sorting of lysosomal membrane and soluble proteins. Protein sorting to the yeast vacuole/lysosome provides a simple model system to study this process. We have mapped the first sorting signal in a vacuolar membrane protein, repressible alkaline phosphatase, and have shown it to be both necessary and sufficient for vacuolar delivery of this enzyme. The sorting information is confined to the transmembrane and cytoplasmic tail region of this type II integral membrane protein. The location of this sorting signal provides an explanation for some of the differences observed between membrane and soluble vacuolar protein sorting.