Investigation of Ldb19/Art1 localization and function at the late Golgi

Martínez-Márquez, Jorge Y.; Duncan, Mara C.

doi:10.1371/journal.pone.0206944

Cited by 8 publications

(9 citation statements)

References 64 publications

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“…In diploid cells, Gga2 is important for genotoxic stress resistance and diploid cells lacking Gga2 exhibit high levels of genomic instability (Krol et al., 2015). Moreover, deletion of GGA2 shows complete synthetic lethality with mutation of the arrestin LDB19 , suggesting that Gga1 is unable to compensate for Gga2 for one or more critical functions (Zhao et al., 2013; Martinez‐Marquez and Duncan, 2018). Although it remains to be determined the extent to which loss of GGA2 alone impairs the degradation of cell surface proteins, deletion of GGA2 disrupts the vacuolar protein sorting of the siderophore transporters Sit1, and Arn1 suggesting that this may be a general effect (Kim et al., 2007; Erpapazoglou et al., 2008; Deng et al., 2009).…”

Section: Discussionmentioning

confidence: 99%

Plasma membrane to vacuole traffic induced by glucose starvation requires Gga2‐dependent sorting at the trans‐Golgi network

Buelto

Hung

Aoh

et al. 2020

Biology of the Cell

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Background Information. In the yeast Saccharomyces cerevisiae, acute glucose starvation induces rapid endocytosis followed by vacuolar degradation of many plasma membrane proteins. This process is essential for cell viability, but the regulatory mechanisms that control it remain poorly understood. Under normal growth conditions, a major regulatory decision for endocytic cargo occurs at the trans-Golgi network (TGN) where proteins can recycle back to the plasma membrane or can be recognized by TGN-localised clathrin adaptors that direct them towards the vacuole. However, glucose starvation reduces recycling and alters the localization and post-translational modification of TGN-localised clathrin adaptors. This raises the possibility that during glucose starvation endocytosed proteins are routed to the vacuole by a novel mechanism that bypasses the TGN or does not require TGN-localised clathrin adaptors. Results. Here, we investigate the role of TGN-localised clathrin adaptors in the traffic of several amino acid permeases, including Can1, during glucose starvation. We find that Can1 transits through the TGN after endocytosis in both starved and normal conditions. Can1 and other amino acid permeases require TGN-localised clathrin adaptors for maximal delivery to the vacuole. Furthermore, these permeases are actively sorted to the vacuole, because ectopically forced de-ubiquitination at the TGN results in the recycling of the Tat1 permase in starved cells. Finally, we report that the Mup1 permease requires the clathrin adaptor Gga2 for vacuolar delivery. In contrast, the clathrin adaptor protein complex AP-1 plays a minor role, potentially in retaining permeases in the TGN, but it is otherwise dispensable for vacuolar delivery. Conclusions and significance. This work elucidates one membrane trafficking pathway needed for yeast to respond to acute glucose starvation. It also reveals the functions of TGNlocalised clathrin adaptors in this process. Our results indicate that the same machinery is needed for vacuolar protein sorting at the GN in glucose starved cells as is needed in the presence of glucose. In addition, our findings provide further support for the model that the TGN is a transit point for many endocytosed proteins, and that Gga2 and AP-1 function in distinct pathways at the TGN.

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Section: Discussionmentioning

confidence: 99%

Plasma membrane to vacuole traffic induced by glucose starvation requires Gga2‐dependent sorting at the trans‐Golgi network

Buelto

Hung

Aoh

et al. 2020

Biology of the Cell

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“…ART–Rsp5 complexes are sometimes sequentially activated, and can act at different internal compartments to regulate the fate of nutrient transporters along the endocytic pathway [Soetens et al., 2001; O'Donnell et al., 2010; Becuwe and Léon, 2014; Hager et al., 2018; Hovsepian et al., 2018; Martínez‐Márquez and Duncan, 2018]. Art1 can re‐localise from the cytosol and/or the trans‐Golgi network (TGN) to the plasma membrane in response to endocytic signals [MacGurn et al., 2011; Baile et al., 2019].…”

Section: Localisation Of Art–rsp5 Complexesmentioning

confidence: 99%

“…While both Bul1 and Art4 can mediate Jen1-ubiquitination at the plasma membrane to initiate endocytosis, Art4 at the TGN is essential for the subsequent post-endocytic sorting of Jen1 into the MVB pathway [Becuwe et al, 2012b;Becuwe and Léon, 2014;Hovsepian et al, 2018]. The role of ART proteins in protein sorting at the TGN is also supported by early work on Bul1 and Bul2 [Helliwell et al, 2001] and a more recent study on Art1 [Martínez-Márquez and Duncan, 2018]. How ARTs are recruited to their site of action is not fully understood.…”

Section: Localisation Of Art-rsp5 Complexesmentioning

confidence: 99%

The α‐arrestin family of ubiquitin ligase adaptors links metabolism with selective endocytosis

Kahlhofer¹,

Léon

Teis³

et al. 2021

Biology of the Cell

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The regulation of nutrient uptake into cells is important, as it allows to either increase biomass for cell growth or to preserve homoeostasis. A key strategy to adjust cellular nutrient uptake is the reconfiguration of the nutrient transporter repertoire at the plasma membrane by the addition of nutrient transporters through the secretory pathway and by their endocytic removal. In this review, we focus on the mechanisms that regulate selective nutrient transporter endocytosis, which is mediated by the α‐arrestin protein family. In the budding yeast Saccharomyces cerevisiae, 14 different α‐arrestins (also named arrestin‐related trafficking adaptors, ARTs) function as adaptors for the ubiquitin ligase Rsp5. They instruct Rsp5 to ubiquitinate subsets of nutrient transporters to orchestrate their endocytosis. The ART proteins are under multilevel control of the major nutrient sensing systems, including amino acid sensing by the general amino acid control and target of rapamycin pathways, and energy sensing by 5′‐adenosine‐monophosphate‐dependent kinase. The function of the six human α‐arrestins is comparably under‐characterised. Here, we summarise the current knowledge about the function, regulation and substrates of yeast ARTs and human α‐arrestins, and highlight emerging communalities and general principles.

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“…Accumulating evidence supports that the specificity of Rsp5 towards its target membrane proteins is dictated by these alpha-arrestins. Specifically, the ability of these proteins to interact with their targets or Rsp5 itself is thought to be regulated by their ubiquitylation [ 15 , 16 , 17 , 18 , 19 ] and phosphorylation status [ 16 , 20 , 21 , 22 ]. The latter has also been suggested to control the topology of the ARTs [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…Notable is the presence of “acidic patch” sequences in the cytosolic N- and/or C-termini of transporters, suggested to act as recognition sites by several alpha-arrestins [ 30 , 32 ]. Moreover, alpha-arrestins not only act at the plasma membrane, but also at the trans-Golgi network (TGN) or even endosomes [ 20 , 21 , 22 , 29 ]. Furthermore, evidence suggests that de-ubiquitylation of transporters by specific enzymes might promote their recycling back to the plasma membrane via the TGN [ 19 , 35 , 36 , 37 , 38 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

The Bul1/2 Alpha-Arrestins Promote Ubiquitylation and Endocytosis of the Can1 Permease upon Cycloheximide-Induced TORC1-Hyperactivation

Megarioti

Primo

Kapetanakis

et al. 2021

IJMS

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Selective endocytosis followed by degradation is a major mechanism for downregulating plasma membrane transporters in response to specific environmental cues. In Saccharomyces cerevisiae, this endocytosis is promoted by ubiquitylation catalyzed by the Rsp5 ubiquitin-ligase, targeted to transporters via adaptors of the alpha-arrestin family. However, the molecular mechanisms of this targeting and their control according to conditions remain incompletely understood. In this work, we dissect the molecular mechanisms eliciting the endocytosis of Can1, the arginine permease, in response to cycloheximide-induced TORC1 hyperactivation. We show that cycloheximide promotes Rsp5-dependent Can1 ubiquitylation and endocytosis in a manner dependent on the Bul1/2 alpha-arrestins. Also crucial for this downregulation is a short acidic patch sequence in the N-terminus of Can1 likely acting as a binding site for Bul1/2. The previously reported inhibition by cycloheximide of transporter recycling, from the trans-Golgi network to the plasma membrane, seems to additionally contribute to efficient Can1 downregulation. Our results also indicate that, contrary to the previously described substrate-transport elicited Can1 endocytosis mediated by the Art1 alpha-arrestin, Bul1/2-mediated Can1 ubiquitylation occurs independently of the conformation of the transporter. This study provides further insights into how distinct alpha-arrestins control the ubiquitin-dependent downregulation of a specific amino acid transporter under different conditions.

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Investigation of Ldb19/Art1 localization and function at the late Golgi

Cited by 8 publications

References 64 publications

Plasma membrane to vacuole traffic induced by glucose starvation requires Gga2‐dependent sorting at the trans‐Golgi network

Plasma membrane to vacuole traffic induced by glucose starvation requires Gga2‐dependent sorting at the trans‐Golgi network

The α‐arrestin family of ubiquitin ligase adaptors links metabolism with selective endocytosis

The Bul1/2 Alpha-Arrestins Promote Ubiquitylation and Endocytosis of the Can1 Permease upon Cycloheximide-Induced TORC1-Hyperactivation

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