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Vol. 14, Issue 2, 477-490, February 2003
and
*University of Michigan, Department of Molecular, Cellular
and Developmental Biology, the Department of Biological Chemistry and
Life Sciences Institute, Ann Arbor, Michigan 48109;
Macroautophagy is a catabolic membrane trafficking phenomenon that
is observed in all eukaryotic cells in response to various stimuli,
such as nitrogen starvation and challenge with specific hormones. In
the yeast Saccharomyces cerevisiae, the induction of
autophagy involves a direct signal transduction mechanism that affects
membrane dynamics. In this system, the induction process modifies a
constitutive trafficking pathway called the cytoplasm-to-vacuole targeting (Cvt) pathway, which transports the vacuolar hydrolase aminopeptidase I, from the formation of small Cvt
vesicles to the formation of autophagosomes. Apg1 is one of the
proteins required for the direct signal transduction cascade that
modifies membrane dynamics. Although Apg1 is required for both the Cvt
pathway and autophagy, we find that Apg1 kinase activity is required
only for Cvt trafficking of aminopeptidase I but not
for import via autophagy. In addition, the data support a novel role
for Apg1 in nucleation of autophagosomes that is distinct from its
catalytic kinase activity and imply a qualitative difference in the
mechanism of autophagosome and Cvt vesicle formation.
Department of Cellular and Molecular
Pharmacology, University of California, San Francisco, San Francisco,
California 94143; and University of Florida
College of Medicine, Department of Anatomy and Cell Biology,
Gainesville, Florida 32610
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