Apg9p/Cvt7p Is an Integral Membrane Protein Required for Transport Vesicle Formation in the Cvt and Autophagy Pathways

doi:10.1083/jcb.148.3.465

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© The Rockefeller University Press, 0021-9525/2000//465 $5.00
The Journal of Cell Biology, Volume 148, Number 3, , 2000 465-480

Original Article

Apg9p/Cvt7p Is an Integral Membrane Protein Required for Transport Vesicle Formation in the Cvt and Autophagy Pathways

Takeshi Noda^a, John Kim^b, Wei-Pang Huang^b, Misuzu Baba^c, Chikara Tokunaga^a, Yoshinori Ohsumi^a, and Daniel J. Klionsky^b

^a Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan
^b Section of Microbiology, University of California, Davis, California 95616
^c Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, Tokyo 112, Japan
Section of Microbiology, University of California, Davis, CA 95616.(530) 752-9014(530) 752-0277

djklionsky{at}ucdavis.edu

In nutrient-rich, vegetative conditions, the yeast Saccharomycescerevisiae transports a resident protease, aminopeptidase I(API), to the vacuole by the cytoplasm to vacuole targeting(Cvt) pathway, thus contributing to the degradative capacityof this organelle. When cells subsequently encounter starvationconditions, the machinery that recruited precursor API (prAPI)also sequesters bulk cytosol for delivery, breakdown, and recyclingin the vacuole by the autophagy pathway. Each of these overlappingalternative transport pathways is specifically mobilized dependingon environmental cues. The basic mechanism of cargo packagingand delivery involves the formation of a double-membrane transportvesicle around prAPI and/or bulk cytosol. Upon completion, theseCvt and autophagic vesicles are targeted to the vacuole to allowdelivery of their lumenal contents.

Key questions remain regarding the origin and formation of thetransport vesicle. In this study, we have cloned the APG9/CVT7gene and characterized the gene product. Apg9p/Cvt7p is thefirst characterized integral membrane protein required for Cvtand autophagy transport. Biochemical and morphological analysesindicate that Apg9p/Cvt7p is localized to large perivacuolarpunctate structures, but does not colocalize with typical endomembranemarker proteins. Finally, we have isolated a temperature conditionalallele of APG9/CVT7 and demonstrate the direct role of Apg9p/Cvt7pin the formation of the Cvt and autophagic vesicles. From theseresults, we propose that Apg9p/Cvt7p may serve as a marker fora specialized compartment essential for these vesicle-mediatedalternative targeting pathways.

Key Words: aminopeptidase I • lysosome • protein targeting • vacuole • yeast

Takeshi Noda and John Kim contributed equally to this work.

Abbreviations used in this paper: API, aminopeptidase I; CPY,carboxypeptidase Y; Cvt, cytoplasm to vacuole targeting; endoH, endoglycosidase H; GFP, green fluorescent protein; ORF, openreading frame; PGK, phosphoglycerate kinase; prAPI, precursorAPI.

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Reggiori, F., Klionsky, D. J. (2002). Autophagy in the Eukaryotic Cell. Eukaryot Cell 1: 11-21 [Full Text]
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Abeliovich, H., Klionsky, D. J. (2001). Autophagy in Yeast: Mechanistic Insights and Physiological Function. Microbiol. Mol. Biol. Rev. 65: 463-479 [Abstract] [Full Text]
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Leber, R., Silles, E., Sandoval, I. V., Mazon, M. J. (2001). Yol082p, a Novel CVT Protein Involved in the Selective Targeting of Aminopeptidase I to the Yeast Vacuole. J. Biol. Chem. 276: 29210-29217 [Abstract] [Full Text]
Wang, C.-W., Kim, J., Huang, W.-P., Abeliovich, H., Stromhaug, P. E., Dunn, W. A. Jr., Klionsky, D. J. (2001). Apg2 Is a Novel Protein Required for the Cytoplasm to Vacuole Targeting, Autophagy, and Pexophagy Pathways. J. Biol. Chem. 276: 30442-30451 [Abstract] [Full Text]
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