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PMID: 12479808 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Mechanism of cargo selection in the cytoplasm to vacuole targeting pathway.

Developmental cell ·Vol. 3 ·No. 6 ·2002-12-00 ·Pages 825-37

Shintani T, Huang WP, Stromhaug PE, Klionsky DJ

Abstract

The proper functioning of eukaryotic organelles is largely dependent on the specific packaging of cargo proteins within transient delivery vesicles. The cytoplasm to vacuole targeting (Cvt) pathway is an autophagy-related trafficking pathway whose cargo proteins, aminopeptidase I and alpha-mannosidase, are selectively transported from the cytoplasm to the lysosome-like vacuole in yeast. This study elucidates a molecular mechanism for cargo specificity in this pathway involving four discrete steps. The Cvt19 receptor plays a central role in this process: distinct domains in Cvt19 recognize oligomerized cargo proteins and link them to the vesicle formation machinery via interaction with Cvt9 and Aut7. Because autophagy is the primary mechanism for organellar turnover, these results offer insights into physiological processes that are critical in cellular homeostasis, including specific packaging of damaged or superfluous organelles for lysosomal delivery and breakdown.

MeSH Terms
Aminopeptidases/genetics,metabolism Autophagy/physiology Autophagy-Related Proteins Carrier Proteins/genetics,metabolism Cell Compartmentation/physiology Cytoplasm/drug effects,metabolism,ultrastructure Green Fluorescent Proteins Luminescent Proteins Mannosidases/genetics,metabolism Mutation/genetics Peptides/metabolism Phagosomes/drug effects,metabolism,ultrastructure Protein Structure, Secondary/physiology Protein Structure, Tertiary/physiology Protein Transport/drug effects,physiology Receptors, Cell Surface/metabolism Recombinant Fusion Proteins Saccharomyces cerevisiae/cytology,drug effects,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism Signal Transduction/physiology Transport Vesicles/drug effects,metabolism,ultrastructure Vacuoles/drug effects,metabolism,ultrastructure Vesicular Transport Proteins alpha-Mannosidase
Chemicals
ATG19 protein, S cerevisiae Autophagy-Related Proteins Carrier Proteins Luminescent Proteins Peptides Receptors, Cell Surface Recombinant Fusion Proteins Saccharomyces cerevisiae Proteins Vesicular Transport Proteins Green Fluorescent Proteins Mannosidases alpha-Mannosidase Aminopeptidases APE1 protein, S cerevisiae
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Shintani Takahiro
University of Michigan, Department of Molecular, Cellular, and Developmental Biology, Ann Arbor 48109, USA.
Huang Wei-Pang
Stromhaug Per E
Klionsky Daniel J
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32 references, click to expand
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Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1534-5807
Published
2002-12-00
Pages
825-37
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC2737732
Subset
IM
Grants
NIGMS NIH HHS · R01 GM053396 · United States
NIGMS NIH HHS · R01 GM053396-12 · United States
NIGMS NIH HHS · R01 GM053396-13 · United States
NIGMS NIH HHS · GM53396 · United States
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