Glut1-mediated glucose transport regulates HIV infection

Loisel-Meyer, Séverine; Swainson, Louise; Craveiro, Marco; Oburoglu, Leal; Mongellaz, Cédric; Costa, Caroline; Martinez, Marion; Cosset, François‐Loïc; Battini, Jean-Luc; Herzenberg, Leonard A.; Herzenberg, Leonore A.; Atkuri, Kondala R.; Sitbon, Marc; Kinet, Sandrina; Verhoeyen, Els; Taylor, Naomi

doi:10.1073/pnas.1121427109

Cited by 125 publications

(128 citation statements)

References 52 publications

(53 reference statements)

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“…Studies by other groups clearly established that neutrophils are avid consumers of glucose (40) and that the upregulation of surface Glut1 expression is associated with neutrophil activation upon exposure to inflammatory conditions (41). A similar increase in glucose-dependent metabolism is seen in other activated leukocyte subsets, notably T and B cells (29,(42)(43)(44)(45). In contrast with Glut1, expression of the amino acid transporter ASCT2 is not uniformly increased on CF airway neutrophils (decreased on A1 and increased on A2 neutrophils compared with blood neutrophils, respectively).…”

Section: Discussionmentioning

confidence: 73%

Metabolic Adaptation of Neutrophils in Cystic Fibrosis Airways Involves Distinct Shifts in Nutrient Transporter Expression

Laval

Touhami

Herzenberg

et al. 2013

The Journal of Immunology

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Inflammatory conditions can profoundly alter human neutrophils, a leukocyte subset generally viewed as terminally differentiated and catabolic. In cystic fibrosis (CF) patients, neutrophils recruited to CF airways show active exocytosis and sustained phosphorylation of prosurvival, metabolic pathways. Because the CF airway lumen is also characterized by high levels of free glucose and amino acids, we compared surface expression of Glut1 (glucose) and ASCT2 (neutral amino acids) transporters, as well as that of PiT1 and PiT2 (inorganic phosphate transporters), in blood and airway neutrophils, using specific retroviral envelope-derived ligands. Neither nutrient transporter expression nor glucose uptake was altered on blood neutrophils from CF patients compared with healthy controls. Notably, however, airway neutrophils of CF patients had higher levels of PiT1 and Glut1 and increased glucose uptake compared with their blood counterparts. Based on primary granule exocytosis and scatter profiles, CF airway neutrophils could be divided into two subsets, with one of the subsets characterized by more salient increases in Glut1, ASCT2, PiT1, and PiT2 expression. Moreover, in vitro exocytosis assays of blood neutrophils suggest that surface nutrient transporter expression is not directly associated with primary (or secondary) granule exocytosis. Although expression of nutrient transporters on CF blood or airway neutrophils was not altered by genotype, age, gender, or Pseudomonas aeruginosa infection, oral steroid treatment decreased Glut1 and PiT2 levels in blood neutrophils. Thus, neutrophils recruited from blood into the CF airway lumen display augmented cell surface nutrient transporter expression and glucose uptake, consistent with metabolic adaptation.

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Section: Discussionmentioning

confidence: 73%

Metabolic Adaptation of Neutrophils in Cystic Fibrosis Airways Involves Distinct Shifts in Nutrient Transporter Expression

Laval

Touhami

Herzenberg

et al. 2013

The Journal of Immunology

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“…[206][207][208] It was observed that increased expression of the GLUT1 gene in interleukin-7-induced T-cells rendered CD4 T-cells and thymocytes susceptible to HIV-1 infection. 206,207 These reports suggest that the GLUT1-mediated metabolic pathway is the major regulator in HIV-infected cells. 207 Thus, GLUT1 could be a potential marker of a diseased heart and inflammation in HIV-infected subjects.…”

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confidence: 99%

“…206,207 These reports suggest that the GLUT1-mediated metabolic pathway is the major regulator in HIV-infected cells. 207 Thus, GLUT1 could be a potential marker of a diseased heart and inflammation in HIV-infected subjects. 40,202,207 Moreover, other GLUTs, such as GLUT4, have been reported to be expressed on the myeloma cell membrane, where it is responsible for cell glucose consumption.…”

mentioning

confidence: 99%

“…207 Thus, GLUT1 could be a potential marker of a diseased heart and inflammation in HIV-infected subjects. 40,202,207 Moreover, other GLUTs, such as GLUT4, have been reported to be expressed on the myeloma cell membrane, where it is responsible for cell glucose consumption. 209 It was also found that GLUT4 expression levels were increased and GLUT2 expression levels were decreased in senescent hepatic cells and chronically diseased human liver tissues, which suggests that GLUT4 may play an important role in liver cirrhosis.…”

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confidence: 99%

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Structure of, and functional insight into the GLUT family of membrane transporters

Long¹,

Cheeseman²

2015

CHC

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This review examines the development of structure and function of the human GLUT proteins, gene family hSLC2A. These proteins are essential for moving the key metabolites, glucose, galactose, and fructose in and out of cells, as well as a number of other important substrates. Despite over five decades of research, it is still not fully understood how they work at the molecular level, although the recent publication of a crystal structure of GLUT1 sug-

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“…Binding of defined ligands allows the quantification of distinct sets of metabolite transporters at the cell surface. [9][10][11][12][13] Furthermore, while cell surface labeling is readily achieved on cultured cell lines and circulating hematopoietic cells, singlecell labeling of solid tumors has remained problematic. Indeed, such analyses require dissociation methods that yield sufficient numbers of viable cells while maintaining the initial cell composition of the tumor.…”

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Optimization of tumor xenograft dissociation for the profiling of cell surface markers and nutrient transporters

Petit

Massonnet

Maciorowski

et al. 2013

Laboratory Investigation

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Metabolic adaptations and changes in the expression of nutrient transporters are known to accompany tumorigenic processes. Nevertheless, in the context of solid tumors, studies of metabolism are hindered by a paucity of tools allowing the identification of cell surface transporters on individual cells. Here, we developed a method for the dissociation of human breast cancer tumor xenografts combined with quantification of cell surface markers, including metabolite transporters. The expression profiles of four relevant nutrient transporters for cancer cells' metabolism, Glut1, ASCT2, PiT1 and PiT2 (participating to glucose, glutamine and inorganic phosphate, respectively), as detected by new retroviral envelope glycoprotein-derived ligands, were distinctive of each tumor, unveiling underlying differences in metabolic pathways. Our tumor dissociation procedure and nutrient transporter profiling technology provides opportunities for future basic research, clinical diagnosis, prognosis and evaluation of therapeutic responses, as well as for drug discovery and development. Markers of tumor cell metabolism are of valuable importance for basic and clinical cancer research. The identification of metabolic alterations that accompany cancer processes is becoming critical for refining the clinical evaluation and treatment of patients, 1,2 as well as for further drug discovery and development. While metabolomics relies mainly on the quantification of anabolic and catabolic end products, 3 the bidirectional fluxes of nutrients and metabolites, as well as the efflux of toxins and pharmaceutical compounds, are ensured by nutrient transporters. 4 However, the monitoring of metabolite and nutrient transporters at the cell surface has been hampered by the paucity, if not total lack, of exofacial antibodies to such transporters. 5,6 Cell entry of gamma-and deltaretroviruses occurs via recognition of membrane metabolite transporters by retroviral envelope glycoproteins (Env). 7,8 Viral entry occurs following the specific binding of the amino-terminal receptor binding domain (RBD) of an individual Env with its cognate receptor. We designed RBD probes, derived from gamma-and deltaretroviral Env, as specific ligands that bind to these cell surface transporters. Binding of defined ligands allows the quantification of distinct sets of metabolite transporters at the cell surface. 9-13 Furthermore, while cell surface labeling is readily achieved on cultured cell lines and circulating hematopoietic cells, singlecell labeling of solid tumors has remained problematic. Indeed, such analyses require dissociation methods that yield

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Glut1-mediated glucose transport regulates HIV infection

Cited by 125 publications

References 52 publications

Metabolic Adaptation of Neutrophils in Cystic Fibrosis Airways Involves Distinct Shifts in Nutrient Transporter Expression

Metabolic Adaptation of Neutrophils in Cystic Fibrosis Airways Involves Distinct Shifts in Nutrient Transporter Expression

Structure of, and functional insight into the GLUT family of membrane transporters

Optimization of tumor xenograft dissociation for the profiling of cell surface markers and nutrient transporters

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