Mechanism of cargo selection in the cytoplasm to vacuole targeting pathway.
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.
Shintani
Takahiro
T
University of Michigan, Department of Molecular, Cellular, and Developmental Biology, Ann Arbor 48109, USA.
Huang
Wei-Pang
WP
Stromhaug
Per E
PE
Klionsky
Daniel J
DJ
D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002451:Cell Compartmentation / Q000502:physiology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D008361:Mannosidases / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000378:metabolism; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D017433:Protein Structure, Secondary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D033921:Vesicular Transport Proteins; D043323:alpha-Mannosidase
C434480:ATG19 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D008164:Luminescent Proteins; D010455:Peptides; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D049452:Green Fluorescent Proteins; D008361:Mannosidases; D043323:alpha-Mannosidase; D000626:Aminopeptidases; C019689:APE1 protein, S cerevisiae