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Chapter category: Apoptosis

Cytoplasm to Vacuole Targeting

This chapter appears in the following book:

Autophagy

Edited by: Daniel Klionsky
ISBN: 1-58706-203-8
» Get more information about this book at landesbioscience.com «

Chapter authors:
Per E. Strømhaug and Daniel J. Klionsky

The cytoplasm to vacuole targeting (Cvt) pathway is a biosynthetic membrane transport mechanism for the delivery of the resident enzymes aminopeptidase I (Ape1) and alpha-mannosidase (Ams1) to the vacuole. These hydrolases are synthesized on free ribosomes in the cytosol where they rapidly oligomerize. Precursor Ape1 dodecamers further aggregate into a higher order Ape1 complex that subsequently interacts with the soluble receptor Cvt19. Cvt19 also binds Ams1 oligomers and the resulting structure is called a Cvt complex. The Cvt complex is brought into proximity of a sequestering membrane by the interaction of Cvt19 with Cvt9 and Aut7. A Cvt vesicle is formed in a process that requires the same set of proteins that is used for starvation induced non-selective autophagy. The similarity of the Cvt pathway to autophagy is also demonstrated by the selective uptake of the Cvt complex into autophagosomes during nutrient deprivation. The formation of the Cvt vesicles and autophagosomes requires the membrane protein Apg9, the Apg1 protein kinase complex and the phosphatidylinositol 3-kinase complex I. In addition, the formation of the Cvt vesicles requires phosphatidylinositol(3)phosphate-binding proteins, which are not used by autophagy. Upon completion of the vesicles, the outer membrane of the Cvt vesicle fuses with the vacuolar membrane and a single membrane bound Cvt body is released into the vacuolar lumen. A concerted action of lipases and proteases then liberates alpha-mannosidase and allows the proteolytic maturation and activation of aminopeptidase I dodecamers.

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