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Originally published In Press as doi:10.1074/jbc.M210436200 on November 20, 2002

J. Biol. Chem., Vol. 278, Issue 7, 5009-5020, February 14, 2003
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Vps51 Is Part of the Yeast Vps Fifty-three Tethering Complex Essential for Retrograde Traffic from the Early Endosome and Cvt Vesicle Completion*

Fulvio Reggiori, Chao-Wen Wang, Per E. Stromhaug, Takahiro Shintani, and Daniel J. KlionskyDagger

From the Departments of Molecular, Cellular and Developmental Biology and Biological Chemistry, University of Michigan and the Life Sciences Institute, Ann Arbor, Michigan 48109

Autophagy, pexophagy, and the Cvt pathway are processes that deliver hydrolytic enzymes and substrates to the yeast vacuole/lysosome via double-membrane cytosolic vesicles. Whereas these pathways operate under different nutritional conditions, they all employ common machinery with only a few specific factors assisting in the choice of the delivery program and the membrane source for the sequestering vesicle. We found that the YKR020w gene product is essential for Cvt vesicle formation but not for pexophagy or induction of autophagy. Autophagosomes in the ykr020wDelta mutant, however, have a reduced size. We demonstrate that Ykr020 is a subunit of the Vps fifty-three tethering complex, composed of Vps52, Vps53, and Vps54, which is required for retrograde traffic from the early endosome back to the late Golgi, and for this reason we named it Vps51. This complex participates in a fusion event together with Tlg1 and Tlg2, two SNAREs also shown to be necessary for Cvt vesicle assembly. In particular, those factors are essential to correctly target the prApe1-Cvt19-Cvt9 complex to the preautophagosomal structure, the site of Cvt vesicle formation.


* This work was supported by National Institutes of Health Public Health Service Grant GM53396 (to D. J. K.) and by a European Molecular Biology Organization long-term fellowship (to F. R.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: University of Michigan, Dept. of Molecular, Cellular and Developmental Biology, Ann Arbor, MI 48109-1048. Tel.: 734-615-6556; Fax: 734-647-0884; E-mail: klionsky@umich.edu.


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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