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PMID: 12589048 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Chemical genetic analysis of Apg1 reveals a non-kinase role in the induction of autophagy.

Molecular biology of the cell ·Vol. 14 ·No. 2 ·2003-02-00 ·Pages 477-90

Abeliovich H, Zhang C, Dunn WA, Shokat KM, Klionsky DJ

Abstract

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.

MeSH Terms
Aminopeptidases/metabolism Autophagy Autophagy-Related Proteins Blotting, Western Cell Membrane/metabolism Cell Nucleus/metabolism Centrifugation, Density Gradient Codon Cytoplasm/metabolism Dose-Response Relationship, Drug Green Fluorescent Proteins Immunoglobulin G/metabolism Luminescent Proteins/metabolism Models, Biological Models, Chemical Mutagenesis, Site-Directed Mutation Nitrogen/metabolism Open Reading Frames Phosphates/metabolism Phosphorylation Plasmids/metabolism Precipitin Tests Protein Conformation Protein Kinases/chemistry,genetics Protein Structure, Tertiary Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins/chemistry,genetics Sepharose/chemistry Sirolimus/pharmacology Time Factors Two-Hybrid System Techniques Vacuoles/metabolism
Chemicals
Autophagy-Related Proteins Codon Immunoglobulin G Luminescent Proteins Phosphates Saccharomyces cerevisiae Proteins Green Fluorescent Proteins Sepharose Protein Kinases ATG1 protein, S cerevisiae Aminopeptidases Nitrogen Sirolimus
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Abeliovich Hagai
University of Michigan, Department of Molecular, Cellular and Developmental Biology, Ann Arbor 48109, USA.
Zhang Chao
Dunn William A
Shokat Kevan M
Klionsky Daniel J
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e02-07-0413
Published
2003-02-00
Pages
477-90
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC149986
Subset
IM
Grants
NIAID NIH HHS · R01 AI044009 · United States
NIGMS NIH HHS · R01 GM053396 · United States
NIAID NIH HHS · AI44009 · United States
NIGMS NIH HHS · GM53396 · United States
External Links
PubMed source DOI: 10.1091/mbc.e02-07-0413 PMC Full Text View journal details
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