Hrr25 kinase promotes selective autophagy by phosphorylating the cargo receptor
            <scp>A</scp>
            tg19

Pfaffenwimmer, Thaddaeus; Reiter, Wolfgang; Brach, Thorsten; Nogellova, Veronika; Papinski, Daniel; Schuschnig, Martina; Abert, Christine; Ammerer, Gustav; Martens, Sascha; Kraft, Claudine

doi:10.15252/embr.201438932

Cited by 91 publications

(104 citation statements)

References 36 publications

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“…In parallel with this study, we found that Hrr25 also phosphorylates Ser391 of Atg19, which corresponds to Ser383 of Atg34, to enhance the Atg19-Atg11 interaction, resulting in the stimulation of the Cvt pathway [17]. Similar results were also reported by another group [27]. In addition, we showed that Atg36, a receptor for autophagic degradation of peroxisomes (pexophagy) [30,31], is also phosphorylated by Hrr25 to interact with the common adaptor Atg11 [17].…”

Section: Hrr25 Promotes Atg11 Targeting To the Ams1 Complex By Enhancsupporting

confidence: 90%

“…A recent study identified two phosphorylated residues (Ser382 and Ser383) in the Atg11-binding region of Atg34 by mass spectrometry, and also reported that the simultaneous Ala replacement of these residues abolished autophagic transport of Ams1 [27]. In this study, we showed that the S383A mutation but not the S382A mutation impaired Atg34 transport to the vacuole (Fig.…”

Section: Hrr25 Promotes Atg11 Targeting To the Ams1 Complex By Enhancsupporting

confidence: 67%

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Hrr25 phosphorylates the autophagic receptor Atg34 to promote vacuolar transport of α‐mannosidase under nitrogen starvation conditions

2014

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a b s t r a c tIn Saccharomyces cerevisiae, under nitrogen-starvation conditions, the a-mannosidase Ams1 is recognized by the autophagic receptor Atg34 and transported into the vacuole, where it functions as an active enzyme. In this study, we identified Hrr25 as the kinase that phosphorylates Atg34 under these conditions. Hrr25-mediated phosphorylation does not affect the interaction of Atg34 with Ams1, but instead promotes Atg34 binding to the adaptor protein Atg11, which recruits the autophagy machinery to the Ams1-Atg34 complex, resulting in activation of the vacuolar transport of Ams1. Our findings reveal the regulatory mechanism of a biosynthetic pathway mediated by the autophagy machinery. Structured summary of protein interactions:Hrr25 phosphorylates Atg34 by protein kinase assay (View interaction) Ams1 and Atg34 colocalize by fluorescence microscopy (View interaction) Atg34 physically interacts with Ams1 by anti tag coimmunoprecipitation (View interaction)

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Section: Hrr25 Promotes Atg11 Targeting To the Ams1 Complex By Enhancsupporting

confidence: 90%

Section: Hrr25 Promotes Atg11 Targeting To the Ams1 Complex By Enhancsupporting

confidence: 67%

Hrr25 phosphorylates the autophagic receptor Atg34 to promote vacuolar transport of α‐mannosidase under nitrogen starvation conditions

2014

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“…Several of the Atg proteins are phosphorylated, but until recently it was not known if any of these proteins were Atg1 substrates. Many other protein kinases (i.e., proteins that are not part of the autophagy core machinery) also modulate autophagy activity, [25][26][27][28] but in most cases the relevant targets have not been identified. Atg9 plays a key role in autophagy, and we recently demonstrated that the amount of the Atg9 protein correlates with the rate of autophagosome formation.…”

Section: Determination Of Atg9 Phosphorylation Sitesmentioning

confidence: 99%

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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“…For example, phosphorylation of Atg19 by Hrr25 and of Atg32 by casein kinase 2 is required for their interaction with Atg11. 73,74 Phosphorylation plays dual roles in regulating the scaffolding and kinase functions of ULK1 to coordinate the autophagic response in mammalian cells. 75 In human embryonic kidney (HEK)-293 cells, autophosphorylation at Thr180 within the ULK1 kinase-activation loop is required for sustaining ULK1 kinase activity and its intracellular localization to phagophores upon starvation.…”

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confidence: 99%

Posttranslational modification of autophagy-related proteins in macroautophagy

Xie¹,

et al. 2014

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Macroautophagy is an intracellular catabolic process involved in the formation of multiple membrane structures ranging from phagophores to autophagosomes and autolysosomes. Dysfunction of macroautophagy is implicated in both physiological and pathological conditions. To date, 38 autophagy-related (ATG) genes have been identified as controlling these complicated membrane dynamics during macroautophagy in yeast; approximately half of these genes are clearly conserved up to human, and there are additional genes whose products function in autophagy in higher eukaryotes that are not found in yeast. The function of the ATG proteins, in particular their ability to interact with a number of macroautophagic regulators, is modulated by posttranslational modifications (PTMs) such as phosphorylation, glycosylation, ubiquitination, acetylation, lipidation, and proteolysis. In this review, we summarize our current knowledge of the role of ATG protein PTMs and their functional relevance in macroautophagy. Unraveling how these PTMs regulate ATG protein function during macroautophagy will not only reveal fundamental mechanistic insights into the regulatory process, but also provide new therapeutic targets for the treatment of autophagy-associated diseases.

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Hrr25 kinase promotes selective autophagy by phosphorylating the cargo receptor A tg19

Cited by 91 publications

References 36 publications

Hrr25 phosphorylates the autophagic receptor Atg34 to promote vacuolar transport of α‐mannosidase under nitrogen starvation conditions

Hrr25 phosphorylates the autophagic receptor Atg34 to promote vacuolar transport of α‐mannosidase under nitrogen starvation conditions

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

Posttranslational modification of autophagy-related proteins in macroautophagy

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