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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