Atg27 Is Required for Autophagy-dependent Cycling of Atg9

Yen, Wei-Lien; Legakis, Julie E.; Nair, Usha; Klionsky, Daniel J.

doi:10.1091/mbc.e06-07-0612

Cited by 162 publications

(162 citation statements)

References 41 publications

(68 reference statements)

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“…Atg9 localization to the PAS from the peripheral sites (referred to as anterograde transport) depends on Atg11, Atg23 and Atg27 [63,[87][88][89]. Return to the peripheral sites (retrograde movement) requires Atg1-Atg13, Atg2 and Atg18; PAS recruitment of the latter involves binding to PtdIns3P and thus necessitates the function of Atg14 and the class III PtdIns3K complex [63].…”

Section: Yeast Atg9mentioning

confidence: 99%

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The machinery of macroautophagy

et al. 2013

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Autophagy is a primarily degradative pathway that takes place in all eukaryotic cells. It is used for recycling cytoplasm to generate macromolecular building blocks and energy under stress conditions, to remove superfluous and damaged organelles to adapt to changing nutrient conditions and to maintain cellular homeostasis. In addition, autophagy plays a critical role in cytoprotection by preventing the accumulation of toxic proteins and through its action in various aspects of immunity including the elimination of invasive microbes and its participation in antigen presentation. The most prevalent form of autophagy is macroautophagy, and during this process, the cell forms a double-membrane sequestering compartment termed the phagophore, which matures into an autophagosome. Following delivery to the vacuole or lysosome, the cargo is degraded and the resulting macromolecules are released back into the cytosol for reuse. The past two decades have resulted in a tremendous increase with regard to the molecular studies of autophagy being carried out in yeast and other eukaryotes. Part of the surge in interest in this topic is due to the connection of autophagy with a wide range of human pathophysiologies including cancer, myopathies, diabetes and neurodegenerative disease. However, there are still many aspects of autophagy that remain unclear, including the process of phagophore formation, the regulatory mechanisms that control its induction and the function of most of the autophagy-related proteins. In this review, we focus on macroautophagy, briefly describing the discovery of this process in mammalian cells, discussing the current views concerning the donor membrane that forms the phagophore, and characterizing the autophagy machinery including the available structural information.

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Section: Yeast Atg9mentioning

confidence: 99%

“…Similarly, no structural information has been published for the Atg11, Atg23 and Atg27 proteins, which are involved in Atg9 localization to the PAS [63,[87][88][89] (Figure 3). Atg18, together with Atg2, helps Atg9 cycle from the PAS to peripheral sites [63].…”

Section: Atg9 Complexmentioning

confidence: 99%

The machinery of macroautophagy

et al. 2013

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“…Because of the known role of Atg11, Atg23 and Atg27 in regulating Atg9 movement, 20,46 and based on our finding that the MKO strain expressing these proteins recapitulates the Atg9 localization phenotype seen with the mutant forms of Atg9, we hypothesized that the interaction of Atg9 with Atg23 and/or Atg27 might be affected in the Atg9 mutants (Atg11 is not essential for nonselective autophagy and the deletion of ATG11 has little effect on Phho8D60 activity 47 ). To test this hypothesis, we used the bimolecular fluorescence complementation (BiFC) assay.…”

Section: Phosphorylation Of S122 Regulates Atg9 Through Its Interactimentioning

confidence: 99%

“…18 Thus, Atg9 may move between these peripheral sites and the PAS, and earlier studies have suggested that this cycling of Atg9 is required for autophagosome formation, functioning in some manner to direct membrane to the expanding phagophore. 16,[19][20][21] In mammalian cells, ATG9 also displays dynamic cycling, moving between the trans-Golgi network and endosomes in response to nutritional changes. A subpopulation of ATG9 colocalizes with both LC3, a mammalian homolog of Atg8, and RAB7, a late endosomal protein.…”

Section: Introductionmentioning

confidence: 99%

“…The anterograde movement of Atg9 from peripheral sites to the PAS requires Atg23, Atg27 and Atg11 (the latter is required primarily in selective types of autophagy). 20 The retrograde trafficking of Atg9 from the PAS depends on the Atg1-Atg13 complex, the Atg2-Atg18 complex and the phosphatidylinositol 3-kinase complex. 16,19 Self-interaction of Atg9 is also important for its PAS localization.…”

Section: Introductionmentioning

confidence: 99%

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Phosphorylation of Atg9 regulates movement to the phagophore assembly site and the rate of autophagosome formation

Feng¹,

Backues²,

Baba³

et al. 2016

Autophagy

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Macroautophagy is primarily a degradative process that cells use to break down their own components to recycle macromolecules and provide energy under stress conditions, and defects in macroautophagy lead to a wide range of diseases. Atg9, conserved from yeast to mammals, is the only identified transmembrane protein in the yeast core macroautophagy machinery required for formation of the sequestering compartment termed the autophagosome. This protein undergoes dynamic movement between the phagophore assembly site (PAS), where the autophagosome precursor is nucleated, and peripheral sites that may provide donor membrane for expansion of the phagophore. Atg9 is a phosphoprotein that is regulated by the Atg1 kinase. We used stable isotope labeling by amino acids in cell culture (SILAC) to identify phosphorylation sites on this protein and identified an Atg1-independent phosphorylation site at serine 122. A nonphosphorylatable Atg9 mutant showed decreased autophagy activity, whereas the phosphomimetic mutant enhanced activity. Electron microscopy analysis suggests that the different levels of autophagy activity reflect differences in autophagosome formation, correlating with the delivery of Atg9 to the PAS. Finally, this phosphorylation regulates Atg9 interaction with Atg23 and Atg27.

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Autophagy and Immunity

Liu

Klionsky

2014

Autophagy, Infection, and the Immune Response

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Atg27 Is Required for Autophagy-dependent Cycling of Atg9

Cited by 162 publications

References 41 publications

The machinery of macroautophagy

The machinery of macroautophagy

Phosphorylation of Atg9 regulates movement to the phagophore assembly site and the rate of autophagosome formation

Autophagy and Immunity

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