ABSTRACT
The yeast vacuole is an intracellular organelle which shares functional characteristics with mammalian lysosomes. Protein sorting to lysosomes, the equivalent of yeast vacuoles, is a well-characterized process. Lysosomal protein sorting has been clarified as a result of investigations of the human genetic disease mucolipidosis II. A disruption in the chromosomal PrA-encoding sequence resulted in the elimination of PrA activity and protein. The vacuolar protein targeting signals are most probably recognized by receptor(s). Gene fusions have also been made between the gene coding for PrA and the gene coding for invertase to identify vacuolar protein-sorting information in the PrA precursor. In order to identify the genes coding for the components of this machinery, mutants affected in vacuolar protein targeting. The fact that proteolytic processing of pro-CPY was prevented implicated an essential role of PrA in the activation of vacuolar proteins. The amino terminus of the mature protein appears at residue 77 relative to the initiation codon.
