Multilevel regulation of an α-arrestin by glucose depletion controls hexose transporter endocytosis

Hovsepian, Junie; Defenouillère, Quentin; Albanèse, Véronique; Váchová, Libuše; Garcia, Camille; Palková, Zdena; Léon, Sébastien

doi:10.1083/jcb.201610094

Cited by 59 publications

(82 citation statements)

References 114 publications

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“…Furthermore, and again consistent with broader control of endocytic traffic, AMPK activation promotes macropinocytosis, providing a form of enhanced nutrient uptake . In yeast, ATP levels regulate the localization of clathrin adaptor proteins (APs) to the TGN and endosomes in an AMPK‐dependent manner, and AMPK controls the endocytosis of hexose transporters, again supporting the theme of broad control of endocytic traffic by AMPK during metabolic insufficiency.…”

Section: Control Of Endocytic Membrane Traffic By Ampkmentioning

confidence: 63%

Energetic adaptations: Metabolic control of endocytic membrane traffic

Rahmani

Defferrari

Wakarchuk

et al. 2019

Traffic

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Endocytic membrane traffic controls the access of myriad cell surface proteins to the extracellular milieu, and thus gates nutrient uptake, ion homeostasis, signaling, adhesion and migration. Coordination of the regulation of endocytic membrane traffic with a cell's metabolic needs represents an important facet of maintenance of homeostasis under variable conditions of nutrient availability and metabolic demand. Many studies have revealed intimate regulation of endocytic membrane traffic by metabolic cues, from the specific control of certain receptors or transporters, to broader adaptation or remodeling of the endocytic membrane network. We examine how metabolic sensors such as AMP‐activated protein kinase, mechanistic target of rapamycin complex 1 and hypoxia inducible factor 1 determine sufficiency of various metabolites, and in turn modulate cellular functions that includes control of endocytic membrane traffic. We also examine how certain metabolites can directly control endocytic traffic proteins, such as the regulation of specific protein glycosylation by limiting levels of uridine diphosphate N‐acetylglucosamine (UDP‐GlcNAc) produced by the hexosamine biosynthetic pathway. From these ideas emerge a growing appreciation that endocytic membrane traffic is orchestrated by many intrinsic signals derived from cell metabolism, allowing alignment of the functions of cell surface proteins with cellular metabolic requirements. Endocytic membrane traffic determines how cells interact with their environment, thus defining many aspects of nutrient uptake and energy consumption. We examine how intrinsic signals that reflect metabolic status of a cell regulate endocytic traffic of specific proteins, and, in some cases, exert broad control of endocytic membrane traffic phenomena. Hence, endocytic traffic is versatile and adaptable and can be modulated to meet the changing metabolic requirements of a cell.

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Section: Control Of Endocytic Membrane Traffic By Ampkmentioning

confidence: 63%

Energetic adaptations: Metabolic control of endocytic membrane traffic

Rahmani

Defferrari

Wakarchuk

et al. 2019

Traffic

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“…The full analysis is presented in Table S3. Mup1-GFP immunoprecipitation protocol was adapted from (Hovsepian et al, 2017). 50 OD600nm yeast 684 cells were harvested by centrifugation and mechanically disrupted by glass bead lysis (0.75-1 mm) at 685 22 4°C in 500 µl ice-cold RIPA lysis buffer (50 mM Tris-HCl, pH 7.5, 150 mM NaCl (#3957.5, Roth, 686 Germany), 0.1% SDS, 2 mM EDTA (#ED-1KG, Sigma, Austria), 50 mM NaF (#SO0323, Scharlau, 687 Spain), 1% Nonidet P 40 (#74385, Fluka, Germany), 0.5% Na-deoxycholate (#D6750-25G, Sigma, 688 Austria), 1% glycerol) containing protease inhibitors (cOmplete Protease Inhibitor Cocktail 689 (#11697498001, Sigma, Austria), yeast protease inhibitor cocktail (yPIC, #P8215-5ML, Sigma, 690 Austria), 2 mM phenylmethylsulfonyl fluoride (PMSF, #P7626-5G, Sigma, Austria)) and 20 mM N-691 ethylmaleimide (NEM, #E3876-5G, Sigma, Austria) using four cycles of lysis (2 min), each separated 692 by 2 min chilling on ice.…”

Section: Gene Ontology Analysis 647mentioning

confidence: 99%

“…How these modifications help to control the activity of Art2 remains a complex and 488 open questions. Several arrestins were found to be phospho-inhibited in specific conditions (MacGurn 489 et al, 2011, Becuwe et al, 2012b, O'Donnell et al, 2013, Hovsepian et al, 2017, Merhi and André, 490 2012, Llopis-Torregrosa et al, 2016, the common molecular basis of which is unknown. An exciting 491 hypothesis would be that a-arrestin hyper-phosphorylation would add negative charges, and thereby 492 prevent the recognition of acidic patches on transporters through electrostatic repulsion.…”

mentioning

confidence: 99%

Complementary α-arrestin - Rsp5 ubiquitin ligase complexes control selective nutrient transporter endocytosis in response to amino acid availability

Ivashov

Zimmer

Schmidt

et al. 2020

Preprint

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How cells adjust transport across their membranes is incompletely understood. Previously, we have shown that S.cerevisiae broadly re-configures the nutrient transporters at the plasma membrane in response to amino acid availability, through selective endocytosis of sugar- and amino acid transporters (AATs) (Müller et al., 2015). A genome-wide screen now revealed that Art2/Ecm21, a member of the α-arrestin family of Rsp5 ubiquitin ligase adaptors, is required for the simultaneous endocytosis of four AATs and induced during starvation by the general amino acid control pathway. Art2 uses a basic patch to recognize C-terminal acidic sorting motifs in these AATs and instructs Rsp5 to ubiquitinate proximal lysine residues. In response to amino acid excess, Rsp5 instead uses TORC1-activated Art1 to detect N-terminal acidic sorting motifs within the same AATs, which initiates exclusive substrate-induced endocytosis of individual AATs. Thus, amino acid availability activates complementary α-arrestin-Rsp5-complexes to control selective endocytosis for nutrient acquisition.

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“…When glucose starved cells are returned to glucose, alternative carbon transporters are endocytosed and rely on ubiquitination for degradation, which is provided by spatially distinct, cognate Arrestin-related Trafficking Adaptors (ARTs) at the surface and endolysosomal system (Becuwe et al, 2012;Becuwe and Léon, 2014;Hovsepian et al, 2018). Recent work has also shown how high affinity glucose transporters, which are not required during glucose starvation, are specifically endocytosed and degraded via Rsp5 and the Csr2 ART adaptor, which is repressed by Mig1/Mig2 in glucose rich conditions (Hovsepian et al, 2017). It is less clear if such transcriptional and post-translational regulatory mechanisms described for these sugar transporters during glucose starvation also control other surface membrane proteins.…”

Section: Introductionmentioning

confidence: 99%

A glucose starvation response governs endocytic trafficking and eisosomal retention of surface cargoes

Laidlaw

Bisinski

Shashkova

et al. 2020

Preprint

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Eukaryotic cells adapt their metabolism to the extracellular environment. Downregulation of surface cargo proteins in response to nutrient stress reduces the burden of anabolic processes whilst elevating catabolic production in the lysosome. We use yeast to show that glucose starvation triggers a transcriptional response that simultaneously increases internalisation from the plasma membrane whilst supressing recycling from endosomes back to the surface. Nuclear export of the Mig1 transcriptional repressor in response to glucose starvation increases levels of the Yap1801/02 clathrin adaptors, which is sufficient to increase cargo internalisation. We also show Gpa1, which coordinates endosomal lipid homeostasis, is required for surface recycling of cargo. Nuclear translocation of Mig1 increases GPA2 levels and inhibits recycling, potentially by diverting Gpa1 to the surface and interfering with its endosomal role in recycling. Finally, we show glucose starvation results in transcriptional upregulation of many eisosomal factors, which serve to sequester a portion of nutrient transporters to persist the starvation period and maximise nutrient uptake upon return to replete conditions. This latter mechanism provides a physiological benefit for cells to rapidly recover from glucose starvation. Collectively, this remodelling of the surface protein landscape during glucose starvation calibrates metabolism to available nutrients.

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Multilevel regulation of an α-arrestin by glucose depletion controls hexose transporter endocytosis

Cited by 59 publications

References 114 publications

Energetic adaptations: Metabolic control of endocytic membrane traffic

Energetic adaptations: Metabolic control of endocytic membrane traffic

Complementary α-arrestin - Rsp5 ubiquitin ligase complexes control selective nutrient transporter endocytosis in response to amino acid availability

A glucose starvation response governs endocytic trafficking and eisosomal retention of surface cargoes

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