Aminopeptidase I Is Targeted to the Vacuole by a Nonclassical Vesicular Mechanism

doi:10.1083/jcb.138.1.37

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© The Rockefeller University Press, 0021-9525/1997//37 $5.00
The Journal of Cell Biology, Volume 138, Number 1, , 1997 37-44

Article

Aminopeptidase I Is Targeted to the Vacuole by a Nonclassical Vesicular Mechanism

Sidney V. Scott^*, Misuzu Baba, Yoshinori Ohsumi, and Daniel J. Klionsky^*

^* Section of Microbiology, University of California, Davis, California 95616; Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, Tokyo 112, Japan; and Department of Cell Biology, National Institute for Basic Biology, Okazaki 444, Japan

The yeast vacuolar protein aminopeptidase I (API) is synthesizedas a cytosolic precursor that is transported to the vacuoleby a nonclassical targeting mechanism. Recent genetic studiesindicate that the biosynthetic pathway that transports APIuses many of the same molecular components as the degradative autophagy pathway. This overlap coupled with both in vitroand in vivo analysis of API import suggested that, like autophagy,API transport is vesicular. Subcellular fractionation experimentsdemonstrate that API precursor (prAPI) initially enters a nonvacuolarcytosolic compartment. In addition, subvacuolar vesicles containingprAPI were purified from a mutant strain defective in breakdownof autophagosomes, further indicating that prAPI enters thevacuole inside a vesicle. The purified subvacuolar vesiclesdo not appear to contain vacuolar marker proteins. ImmunogoldEM confirms that prAPI is localized in cytosolic and in subvacuolar vesicles in a mutant strain defective in autophagic body degradation.These data suggest that cytosolic vesicles containing prAPIfuse with the vacuole to release a membrane-bounded intermediatecompartment that is subsequently broken down, allowing APImaturation.

1. Abbreviations used in this paper: ALP, alkaline phosphatase;API, aminopeptidase I; prAPI, API precursor; CPY, carboxypeptidaseY; HD, high density; LD, low density; PGK, phosphoglyceratekinase; PrA, proteinase A; PrB, proteinase B; SV, subvacuolarvesicle; VV, vacuolar vesicle; V, vacuole fraction; I, intermediatefraction; P, pellet fraction; Vps, vacuolar protein sorting.

Please address all correspondence to Daniel J. Klionsky, Sectionof Microbiology, University of California, Davis, CA 95616.Tel.: (916) 752-0277. Fax: (916) 752-9014.

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