Mechanism of Cargo Selection in the Cytoplasm to Vacuole Targeting Pathway

Shintani, Takahiro; Huang, Wei Pang; Strømhaug, Per E.; Klionsky, Daniel J.

doi:10.1016/s1534-5807(02)00373-8

Cited by 332 publications

(481 citation statements)

References 33 publications

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“…Atg8 is an ubiquitin-like protein that is conjugated to phosphatidylethanolamine (Kirisako et al, 1999; and is one of two Atg proteins that remain associated with the completed autophagosome membrane. Similar to Pex14-GFP, Atg8 is degraded after delivery into the vacuole, whereas the GFP moiety is again relatively stable (Shintani et al, 2002). Wildtype, atg1⌬, and atg27⌬ cells were transformed with a plasmid-based GFP-Atg8, grown in SMD medium and then subjected to nitrogen starvation.…”

Section: Atg27 Is Required For the Cvt Pathway And Pexophagy And For mentioning

confidence: 99%

Atg27 Is Required for Autophagy-dependent Cycling of Atg9

Yen

Legakis

Nair

et al. 2007

MBoC

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162

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Autophagy is a catabolic pathway for the degradation of cytosolic proteins or organelles and is conserved among all eukaryotic cells. The hallmark of autophagy is the formation of double-membrane cytosolic vesicles, termed autophagosomes, which sequester cytoplasm; however, the mechanism of vesicle formation and the membrane source remain unclear. In the yeast Saccharomyces cerevisiae, selective autophagy mediates the delivery of specific cargos to the vacuole, the analog of the mammalian lysosome. The transmembrane protein Atg9 cycles between the mitochondria and the pre-autophagosomal structure, which is the site of autophagosome biogenesis. Atg9 is thought to mediate the delivery of membrane to the forming autophagosome. Here, we characterize a second transmembrane protein Atg27 that is required for specific autophagy in yeast. Atg27 is required for Atg9 cycling and shuttles between the pre-autophagosomal structure, mitochondria, and the Golgi complex. These data support a hypothesis that multiple membrane sources supply the lipids needed for autophagosome formation.

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Section: Atg27 Is Required For the Cvt Pathway And Pexophagy And For mentioning

confidence: 99%

Atg27 Is Required for Autophagy-dependent Cycling of Atg9

Yen

Legakis

Nair

et al. 2007

MBoC

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162

142

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“…The receptor protein Atg19 binds to the propeptide of the Ape1 precursor. Interaction of cargobound Atg19 with Atg11 is required for its PAS localization (Scott et al,2001;Shintani et al, 2002). In pexophagy, the cargo selection mechanism may be organized in a similar way, as Atg11 is required for pexophagy in yeast; however, S. cerevisiae atg19 mutants are not blocked in peroxisome degradation.…”

Section: Molecular Model Of Pexophagy: Steps and Protein Complexesmentioning

confidence: 99%

Autophagy in organelle homeostasis: Peroxisome turnover

Monastyrska

Klionsky

2006

Molecular Aspects of Medicine

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When cells are confronted with an insufficient supply of nutrients in their extracellular fluid, they may begin to cannibalize some of their internal proteins as well as whole organelles for reuse in the synthesis of new components. This process is termed autophagy and it involves the formation of a double-membrane structure within the cell, which encloses the material to be degraded into a vesicle called an autophagosome. The autophagosome subsequently fuses with a lysosome/vacuole whose hydrolytic enzymes degrade the sequestered organelle. Degradation of peroxisomes is a specific type of autophagy, which occurs in a selective manner and has been mostly studied in yeast. Recently, it was reported that a similar selective process of autophagy occurs in mammalian cells with proliferated peroxisomes. Here we discuss characteristics of the autophagy of peroxisomes in mammalian cells and present a comprehensive model of their likely mechanism of degradation on the basis of known and common elements from other systems.

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“…Wild-type, atg14⌬, and vps38⌬ cells were transformed with a plasmid expressing either GFP-Snc1 or GFP-Ape1 ( Lewis et al, 2000;Shintani et al, 2002). We also checked the localization of these two chimeras in the vps34⌬ strain; the vps34⌬ cells are unable to synthesize PtdIns(3)P, and all pathways requiring this lipid are blocked.…”

Section: Molecular Biology Of the Cell 2194mentioning

confidence: 99%

“…Before reaching the late endosome, these proteins pass through the early endosome where some components are recycled back to the cell surface (Hicke et al, 1997;Prescianotto-Baschong and Riezman, 1998;Lewis et al, 2000). The carboxypeptidase Y pathway and endocytosis converge at the endosome where another route, the multivesicular body pathway, delivers both resident enzymes and substrates to the vacuole (Katzmann et al, 2002).There is also an additional route to the vacuole called the cytoplasm to vacuole targeting (Cvt) pathway that mediates the transport of certain vacuolar hydrolases such as aminopeptidase I (Ape1) that form a large cytosolic oligomer after synthesis (Klionsky et al, 1992;Kim et al, 1997;Scott et al, 1997;Shintani et al, 2002). The existence of the Cvt pathway has only been demonstrated in the yeast Saccharomyces cerevisiae.…”

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confidence: 99%

“…It seems that this complex is also involved in PtdIns(3)P synthesis at the early endosomes because its function is essential to recruit sorting nexins to those compartments (Hettema et al, 2003). We decided to analyze prApe1 and Snc1 trafficking in mutant strains that specifically affect the function of one of the two PtdIns 3-kinase complexes to see whether it was possible to distinguish the PAS from early endosomes by the fact that their PtdIns(3)P pools are generated in different ways.Wild-type, atg14⌬, and vps38⌬ cells were transformed with a plasmid expressing either GFP-Snc1 or GFP-Ape1 ( Lewis et al, 2000;Shintani et al, 2002). We also checked the localization of these two chimeras in the vps34⌬ strain; the vps34⌬ cells are unable to synthesize PtdIns(3)P, and all pathways requiring this lipid are blocked.…”

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confidence: 99%

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Early Stages of the Secretory Pathway, but Not Endosomes, Are Required for Cvt Vesicle and Autophagosome Assembly inSaccharomyces cerevisiae

Reggiori

Wang

Nair

et al. 2004

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The Cvt pathway is a biosynthetic transport route for a distinct subset of resident yeast vacuolar hydrolases, whereas macroautophagy is a nonspecific degradative mechanism that allows cell survival during starvation. Yet, these two vacuolar trafficking pathways share a number of identical molecular components and are morphologically very similar. For example, one of the hallmarks of both pathways is the formation of double-membrane cytosolic vesicles that sequester cargo before vacuolar delivery. The origin of the vesicle membrane has been controversial and various lines of evidence have implicated essentially all compartments of the endomembrane system. Despite the analogies between the Cvt pathway and autophagy, earlier work has suggested that the origin of the engulfing vesicle membranes is different; the endoplasmic reticulum is proposed to be required only for autophagy. In contrast, in this study we demonstrate that the endoplasmic reticulum and/or Golgi complex, but not endosomal compartments, play an important role for both yeast transport routes. Along these lines, we demonstrate that Berkeley bodies, a structure generated from the Golgi complex in sec7 cells, are immunolabeled with Atg8, a structural component of autophagosomes. Finally, we also show that none of the yeast t-SNAREs are located at the preautophagosomal structure, the presumed site of double-membrane vesicle formation. Based on our results, we propose two models for Cvt vesicle biogenesis. INTRODUCTIONThe lysosome/vacuole is the major cellular center for degradation, recycling, and storage of biological constituents. Several well-characterized transport routes are implicated in protein delivery to this organelle during normal growth conditions. These pathways are conserved among eukaryotic organisms, but work in the yeast Saccharomyces cerevisiae has had a major impact on their characterization and in the identification of the molecular machinery (Conibear and Stevens, 1998). The route called the alkaline phosphatase pathway provides a direct transport connection between the Golgi complex and the vacuole Piper et al., 1997). A second itinerary from the Golgi complex to the vacuole passes through the late endosome and is known as the carboxypeptidase Y pathway (Piper et al., 1995;Babst et al., 1998;Conibear and Stevens, 1998). These two pathways are required for the biogenesis and maintenance of vacuoles, whereas a third route, endocytosis, has a catabolic function. Endocytosis mediates the downregulation of plasma membrane proteins by delivering them via the late endosome to the vacuole for degradation (Hicke, 1999;Katzmann et al., 2002). Before reaching the late endosome, these proteins pass through the early endosome where some components are recycled back to the cell surface (Hicke et al., 1997;Prescianotto-Baschong and Riezman, 1998;Lewis et al., 2000). The carboxypeptidase Y pathway and endocytosis converge at the endosome where another route, the multivesicular body pathway, delivers both resident enzymes and substrates to the vac...

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Mechanism of Cargo Selection in the Cytoplasm to Vacuole Targeting Pathway

Cited by 332 publications

References 33 publications

Atg27 Is Required for Autophagy-dependent Cycling of Atg9

Atg27 Is Required for Autophagy-dependent Cycling of Atg9

Autophagy in organelle homeostasis: Peroxisome turnover

Early Stages of the Secretory Pathway, but Not Endosomes, Are Required for Cvt Vesicle and Autophagosome Assembly inSaccharomyces cerevisiae

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