Ypt1 recruits the Atg1 kinase to the preautophagosomal structure

Wang, Juan; Menon, Shekar; Yamasaki, Akinori; Chou, Hui‐Ting; Walz, Thomas; Jiang, Yu; Ferro‐Novick, Susan

doi:10.1073/pnas.1302337110

Cited by 113 publications

(150 citation statements)

References 31 publications

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“…Our model might appear to conflict with previous reports that TRAPPIII functions at the PAS in yeast and in forming autophagosome in mammalian cells (Lynch-Day et al, 2010;Kakuta et al, 2012;Lipatova et al, 2012;Huang et al, 2011;Wang et al, 2013). Our model does not necessarily exclude these possibilities, but our results suggest that the direct contribution of TRAPPIII to autophagosome formation is not as large as proposed in those studies.…”

Section: Discussioncontrasting

confidence: 56%

TRAPPIII is responsible for the vesicular transport from early endosomes to the Golgi apparatus that facilitates Atg9 cycling in autophagy

Shirahama-Noda

Kira

Yoshimori

et al. 2013

Journal of Cell Science

115

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SummaryAutophagy is a bulk protein-degradation process that is regulated by many factors. In this study, we quantitatively assessed the contribution of each essential yeast gene to autophagy. Of the contributing factors that we identified, we focused on the TRAPPIII complex, which was recently shown to act as a guanine-nucleotide exchange factor for the Rab small GTPase Ypt1. Autophagy is defective in the TRAPPIII mutant under nutrient-rich conditions (Cvt pathway), but starvation-induced autophagy is only partially affected. Here, we show that TRAPPIII functions at the Golgi complex to receive general retrograde vesicle traffic from early endosomes. Cargo proteins in this TRAPPIII-dependent pathway include Atg9, a transmembrane protein that is essential for autophagy, and Snc1, a SNARE unrelated to autophagy. When cells were starved, further disruption of vesicle movement from late endosomes to the Golgi caused defects in Atg9 trafficking and autophagy. Thus, TRAPPIII-dependent sorting pathways provide Atg9 reservoirs for pre-autophagosomal structure and phagophore assembly sites under nutrient-rich conditions, whereas the late endosome-to-Golgi pathway is added to these reservoirs when nutrients are limited. This clarification of the role of TRAPPIII elucidates how general membrane traffic contributes to autophagy.

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Section: Discussioncontrasting

confidence: 56%

TRAPPIII is responsible for the vesicular transport from early endosomes to the Golgi apparatus that facilitates Atg9 cycling in autophagy

Shirahama-Noda

Kira

Yoshimori

et al. 2013

Journal of Cell Science

115

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“…TRAPPI and TRAPPII participate in ER-to-Golgi and intra-Golgi trafficking, respectively (Cai et al, 2007;Cai et al, 2005;Yamasaki et al, 2009), whereas TRAPPIII is the autophagyspecific GEF for Ypt1. During autophagy, TRAPPIII localizes to the PAS in yeast, to which it appears to be recruited by Atg17 (Lynch-Day et al, 2010;Tan et al, 2013;Wang et al, 2013). Once at this site, TRAPPIII mediates the recruitment of YPT1 Lynch-Day et al, 2010;Wang et al, 2013), which, in its activated GTP-bound form, is thought to recruit Atg1 .…”

Section: How Could Eres Contribute To Autophagosome Formation? Model mentioning

confidence: 99%

“…During autophagy, TRAPPIII localizes to the PAS in yeast, to which it appears to be recruited by Atg17 (Lynch-Day et al, 2010;Tan et al, 2013;Wang et al, 2013). Once at this site, TRAPPIII mediates the recruitment of YPT1 Lynch-Day et al, 2010;Wang et al, 2013), which, in its activated GTP-bound form, is thought to recruit Atg1 . Of further significance, the TRAPPIIIYpt1 module has also been detected in immunopurified Atg9-containing vesicles in yeast , which have been shown to contribute to the generation of the PAS in this organism (Mari et al, 2010;Yamamoto et al, 2012) and could be part of the early PAS or phagophore intermediate observed at the recycling endosomes in mammalian cells (Nair et al, 2011).…”

Section: How Could Eres Contribute To Autophagosome Formation? Model mentioning

confidence: 99%

“…In addition to having a role in the tethering of COPII vesicles to the Golgi and in intraGolgi trafficking, the RAB GTPase Ypt1, the yeast counterpart of mammalian RAB1A, is also involved in autophagy (Huang et al, 2011;Lipatova et al, 2012;Lynch-Day et al, 2010;Wang et al, 2013). The role of Ypt1 in different pathways is finely regulated by three different guanine nucleotide exchange factors (GEFs) that form multifactorial complexes.…”

Section: How Could Eres Contribute To Autophagosome Formation? Model mentioning

confidence: 99%

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ERES: sites for autophagosome biogenesis and maturation?

Sánchez

Ktistakis

Reggiori

2015

Journal of Cell Science

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Autophagosomes are the hallmark of autophagy, but despite their central role in this degradative pathway that involves vesicle transport to lysosomes or vacuoles, the mechanism underlying their biogenesis still remains largely unknown. Our current concepts about autophagosome biogenesis are based on models suggesting that a small autonomous cisterna grows into an autophagosome through expansion at its extremities. Recent findings have revealed that endoplasmic reticulum (ER) exit sites (ERES), specialized ER regions where proteins are sorted into the secretory system, are key players in the formation of autophagosomes. Owing to the morphological connection of nascent autophagosomes with the ER, this has raised several questions that challenge our current perception of autophagosome biogenesis, such as are ERES the compartments where autophagosome formation takes place? What is the functional relevance of this connection? Are these compartments providing essential molecules for the generation of autophagosomes and/or are they structural platforms where these vesicles emerge? In this Hypothesis, we discuss recent data that have implicated the ERES in autophagosome biogenesis and we propose two models to describe the possible role of this compartment at different steps in the process of autophagosome biogenesis. This article is part of a Focus on Autophagosome biogenesis. For further reading, please see related articles: ‘Membrane dynamics in autophagosome biogenesis’ by Sven R. Carlsson and Anne Simonsen (J. Cell Sci. 128, 193-205) and ‘WIPI proteins: essential PtdIns3P effectors at the nascent autophagosome’ by Tassula Proikas-Cezanne et al. (J. Cell Sci. 128, 207-217).

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“…The TRAPPIII complex associates withSec23, an integral component of COPII, and is a GTP Exchange Factor (GEF) of a small GTPase Ypt1 in yeast. Therefore COPII vesicles and Ypt1 are recruited to the PAS, where COPII vesicles supply membrane and Ypt1 regulates vesicular events [50,[74][75][76]. Furthermore, it is proposed that the TRAPPIII complex may also be a tether to facilitate heterotypic fusion between an Atg9 vesicle and a COPII vesicle in the PAS [50,77].…”

Section: Converging On the Pasmentioning

confidence: 99%

Preparing the Membrane for Autophagosome Biogenesis

Wilz

Ge²

2014

Cell Dev Biol

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EditorialAutophagy is a fundamental strategy eukaryotic cells employ for bulk turnover of cytoplasmic components to maintain cellular homeostasis. At the organismal level, autophagy is involved in a variety of physiological processes such as development, metabolism and immunity. Dysfunctional autophagy has been implicated in numerous human disorders including cancer, neurodegeneration, aging, infection and metabolic disease [1][2][3].A key step of autophagy is the formation of a cup-shaped membrane precursor, called the phagophore, that engulfs part of the cytoplasm by membrane expansion to seal into a double membrane vesicle, termed the autophagosome. Fusion of the autophagosome with the lysosome leads to the degradation of the cytoplasmic components followed by release of the hydrolyzed products for material recycling [4][5][6][7].To build an autophagosome, a hierarchical cascade of the autophagy related(ATG) proteins is required to assemble a cradle, termed the phagophore assembly site (PAS), in a sub-domain of the endoplasmic reticulum (ER) in mammalian cells or near the vacuole (a functional equivalent of the lysosome) in yeast [5,[8][9][10][11][12][13][14]. In addition, substantial membrane mobilization from multiple locations, including ATG9-vesicles, the Golgi, the ER-Golgi intermediate compartment (ERGIC), ER exit sites(ERES), the plasma membrane (PM) and mitochondria, is necessary to deliver lipids and protein components to the PAS for autophagy initiation and phagophore growth [6,15,16]. Below, we briefly discuss the latest knowledge about how membranes are mobilized under autophagic conditions as well as how these membranes converge in the PAS for nucleating the phagophore precursor. Mobilizing the ATG9 vesiclesAutophagosome biogenesis begins with a membrane nucleation step at the PAS [12,14]. One factor essential for phagophore nucleation is ATG9, a multiple transmembrane protein [17][18][19][20]. In yeast, Atg9 cycles between the Trans-Golgi Network (TGN), mitochondria, the PAS and some distinct tubulovesicular peripheral structures [21][22][23][24][25]. Under starvation conditions, these peripheral compartments become highly dynamic reflecting an increased membrane exchange between these structures and the PAS [25]. Mobilization of Atg9 vesicles from the TGN to the peripheral structures is crucial for subsequent delivery of Atg9 vesicles to the PAS for phagophore nucleation [24,25]. This process requires protein complex formation of Atg9 with two partners, Atg23 and Atg27, as well as the self-dimerization of Atg9 [25][26][27][28]. It has been proposed that proper stoichiometric formation of the Atg9/ Atg23/Atg27 complex facilitates the clustering and sorting of Atg9 into a specific sub-domain in the TGN, which is essential for the generation of the tubulovesicular structure as an intermediate station for the delivery of Atg9 to the PAS [27].A similar cycling of ATG9 between the TGN and certain peripheral compartments also occurs in mammalian cells [29]. These peripheral structures are a combinatio...

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Ypt1 recruits the Atg1 kinase to the preautophagosomal structure

Cited by 113 publications

References 31 publications

TRAPPIII is responsible for the vesicular transport from early endosomes to the Golgi apparatus that facilitates Atg9 cycling in autophagy

TRAPPIII is responsible for the vesicular transport from early endosomes to the Golgi apparatus that facilitates Atg9 cycling in autophagy

ERES: sites for autophagosome biogenesis and maturation?

Preparing the Membrane for Autophagosome Biogenesis

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