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Vol. 10, Issue 5, 1337-1351, May 1999
Section of Microbiology, University of California, Davis,
California 95616
Proper functioning of organelles necessitates efficient protein
targeting to the appropriate subcellular locations. For example, degradation in the fungal vacuole relies on an array of targeting mechanisms for both resident hydrolases and their substrates. The
particular processes that are used vary depending on the available nutrients. Under starvation conditions, macroautophagy is the primary
method by which bulk cytosol is sequestered into autophagic vesicles
(autophagosomes) destined for this organelle. Molecular genetic,
morphological, and biochemical evidence indicates that macroautophagy
shares much of the same cellular machinery as a biosynthetic pathway
for the delivery of the vacuolar hydrolase, aminopeptidase I, via the cytoplasm-to-vacuole
targeting (Cvt) pathway. The machinery required in both pathways
includes a novel protein modification system involving the conjugation
of two autophagy proteins, Apg12p and Apg5p. The conjugation
reaction was demonstrated to be dependent on Apg7p, which shares
homology with the E1 family of ubiquitin-activating enzymes. In this
study, we demonstrate that Apg7p functions at the sequestration step in
the formation of Cvt vesicles and autophagosomes. The subcellular
localization of Apg7p fused to green fluorescent protein (GFP)
indicates that a subpopulation of Apg7pGFP becomes membrane associated
in an Apg12p-dependent manner. Subcellular fractionation experiments also indicate that a portion of the Apg7p pool is pelletable under starvation conditions. Finally, we demonstrate that the Pichia pastoris homologue Gsa7p that is required for peroxisome
degradation is functionally similar to Apg7p, indicating that this
novel conjugation system may represent a general nonclassical targeting
mechanism that is conserved across species.
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S. V. Scott, D. C. Nice III, J. J. Nau, L. S. Weisman, Y. Kamada, I. Keizer-Gunnink, T. Funakoshi, M. Veenhuis, Y. Ohsumi, and D. J. Klionsky Apg13p and Vac8p Are Part of a Complex of Phosphoproteins That Are Required for Cytoplasm to Vacuole Targeting J. Biol. Chem., August 11, 2000; 275(33): 25840 - 25849. [Abstract] [Full Text] [PDF]
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M. U. Hutchins and D. J. Klionsky Vacuolar Localization of Oligomeric alpha -Mannosidase Requires the Cytoplasm to Vacuole Targeting and Autophagy Pathway Components in Saccharomyces cerevisiae J. Biol. Chem., June 1, 2001; 276(23): 20491 - 20498. [Abstract] [Full Text] [PDF]
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R. Leber, E. Silles, I. V. Sandoval, and M. J. Mazon Yol082p, a Novel CVT Protein Involved in the Selective Targeting of Aminopeptidase I to the Yeast Vacuole J. Biol. Chem., July 27, 2001; 276(31): 29210 - 29217. [Abstract] [Full Text] [PDF]
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C.-W. Wang, J. Kim, W.-P. Huang, H. Abeliovich, P. E. Stromhaug, W. A. Dunn Jr., and D. J. Klionsky Apg2 Is a Novel Protein Required for the Cytoplasm to Vacuole Targeting, Autophagy, and Pexophagy Pathways J. Biol. Chem., August 3, 2001; 276(32): 30442 - 30451. [Abstract] [Full Text] [PDF]
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T. Shintani, K. Suzuki, Y. Kamada, T. Noda, and Y. Ohsumi Apg2p Functions in Autophagosome Formation on the Perivacuolar Structure J. Biol. Chem., August 3, 2001; 276(32): 30452 - 30460. [Abstract] [Full Text] [PDF]
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