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Cells carrying a null allele of VPS35 exhibit a differential vacuolar protein sorting defect. The sorting of CPY is drastically affected in !wps35 mutant cells; >95% of CPY is secreted in its Golgi modified p2 precursor form. However, the vast majority of two other soluble vacuolar proteases, proteinase A (Pr A) and proteinase B (PrB) are retained and matured in these mutants, indicating delivery to the vacuole. These results suggest that CPY sorting is completely dependent on the presence of functional Vps35p. Yet the sorting and processing of other soluble hydrolases (PrA and PrB), as well as the vacuolar membrane protein alkaline phosphatase can occur in a Vps35p-independent manner. Apparently only a subset of soluble vacuolar proteins, like CPY, require Vps35p for their efficient sorting to the vacuole. It is possible that CPY and Pr A may utilize different receptor complexes for their sorting and/or delivery to the vacuole.
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