Expression of caveolin‐1 in lymphocytes induces caveolae formation and recruitment of phosphofructokinase to the plasma membrane

Vallejo, Johana; Hardin, Christopher D.

doi:10.1096/fj.04-2380fje

Cited by 25 publications

(23 citation statements)

References 60 publications

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“…Because many metabolic enzymes have been reported to bind to the cell membrane or shuttle between different subcellular localizations to orchestrate a compartmentalization of carbohydrate metabolic pathways (40)(41)(42), it is reasonable to speculate that the modality of glucose transport into the cells (SGLT vs. GLUT) may have the ability to play a role in the determination of the metabolic fate of this important nutrient.…”

Section: Discussionmentioning

confidence: 99%

Functional expression of sodium-glucose transporters in cancer

Scafoglio

Hirayama

Kepe

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

260

249

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Glucose is a major metabolic substrate required for cancer cell survival and growth. It is mainly imported into cells by facilitated glucose transporters (GLUTs). Here we demonstrate the importance of another glucose import system, the sodium-dependent glucose transporters (SGLTs), in pancreatic and prostate adenocarcinomas, and investigate their role in cancer cell survival. Three experimental approaches were used: (i) immunohistochemical mapping of SGLT1 and SGLT2 distribution in tumors; (ii) measurement of glucose uptake in fresh isolated tumors using an SGLT-specific radioactive glucose analog, α-methyl-, which is not transported by GLUTs; and (iii) measurement of in vivo SGLT activity in mouse models of pancreatic and prostate cancer using Me4FDG-PET imaging. We found that SGLT2 is functionally expressed in pancreatic and prostate adenocarcinomas, and provide evidence that SGLT2 inhibitors block glucose uptake and reduce tumor growth and survival in a xenograft model of pancreatic cancer. We suggest that Me4FDG-PET imaging may be used to diagnose and stage pancreatic and prostate cancers, and that SGLT2 inhibitors, currently in use for treating diabetes, may be useful for cancer therapy.SGLT2 | pancreatic cancer | prostate cancer | SGLT2-inhibitors P ancreatic cancer is the fourth-leading cause of cancer-related death in the United States (behind only lung, colon, and breast cancers), with 46,420 estimated new cases in 2014 and a mortality that almost equals incidence (39,590 estimated deaths in 2014); the overall 5-y survival rate is only 7% (seer.cancer.gov/statfacts/html/ pancreas.html). Prostate cancer is the most frequent cancer in men in the United States, with 233,000 estimated new cases in 2014. Despite widespread adoption of screening programs, prostate cancer is still the second-leading cause of cancer-related death in men, second only to lung cancer (seer.cancer.gov/statfacts/html/prost.

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Section: Discussionmentioning

confidence: 99%

Functional expression of sodium-glucose transporters in cancer

Scafoglio

Hirayama

Kepe

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

260

249

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“…The two predominant dynamin-dependent endocytosis uptake routes in cells are caveolar endocytosis and clathrin-mediated endocytosis. Caveolar uptake of HIV-1 in lymphocytes is unlikely, given their paucity of caveolin-1 expression and apparent lack of caveolae (44)(45)(46)(47). Although one study did note caveolin-1 expression in primary CD4 ϩ T cells engaged in virological synapses, viral p24 was not found to colocalize with caveolin-1 (22).…”

Section: Discussionmentioning

confidence: 99%

“…Dynamin-dependent endocytic vesicle scission is predominantly associated with the uptake of endocytic vesicles via clathrin-mediated endocytosis or via caveolae. Since human lymphocytes, including CD4 ϩ T cells, do not express the protein caveolin-1 (cav-1) or bear caveolae (39,(43)(44)(45)(46)(47), we next wanted to investigate whether the dynamin dependence of target cell virus transfer and productive infection that we observed was due to clathrin-mediated, dynamin-dependent endocytosis (38,48). We employed a mix of small-molecule inhibitors of this process and shRNAs directed to the clathrin accessory protein AP180.…”

Section: Virus Coreceptor Binding and Virus-cell Membrane Fusion Occumentioning

confidence: 99%

Productive Entry of HIV-1 during Cell-to-Cell Transmission via Dynamin-Dependent Endocytosis

Sloan

Kuhl

Mésplède

et al. 2013

J Virol

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Canada dHIV-1 can be transmitted as cell-free virus or via cell-to-cell contacts. Cell-to-cell transmission between CD4 ؉ T cells is the more efficient mode of transmission and is predominant in lymphoid tissue, where the majority of virus resides. Yet the cellular mechanisms underlying productive cell-to-cell transmission in uninfected target cells are unclear. Although it has been demonstrated that target cells can take up virus via endocytosis, definitive links between this process and productive infection remain undefined, and this route of transmission has been proposed to be nonproductive. Here, we report that productive cell-to-cell transmission can occur via endocytosis in a dynamin-dependent manner and is sensitive to clathrin-associated antagonists. These data were obtained in a number of CD4 ؉ T-cell lines and in primary CD4 ؉ T cells, using both CXCR4-and CCR5-tropic virus. However, we also found that HIV-1 demonstrated flexibility in its use of such endocytic pathways as certain allogeneic transmissions were seen to occur in a dynamin-dependent manner but were insensitive to clathrin-associated antagonists. Also, depleting cells of the clathrin accessory protein AP180 led to a viral uptake defect associated with enhanced infection. Collectively, these data demonstrate that endosomal uptake of HIV-1 during cell-to-cell transmission leads to productive infection, but they are also indicative of a flexible model of viral entry during cell-to-cell transmission, in which the virus can alter its entry route according to the pressures that it encounters.H IV-1 can be transmitted as free virus or directly between cells via cell-cell contacts. Cell-to-cell transmission is a more efficient and rapid means of viral spread and is the predominant mode of HIV-1 transmission in lymphoid tissue (1, 2). Given that the vast majority of virus within an infected individual is found in lymphoid tissue and in CD4ϩ T cells, cell-to-cell transmission between CD4 ϩ T cells likely represents the most common mode of HIV-1 spread.Improved understanding of the direct and coordinated interactions between T cells and antigen-presenting cells, termed immunological synapses (3), ultimately led to the first description of coordinated retroviral transmission between T cells. Human Tlymphotropic virus type I (HTLV-I) is transmitted via a polarized T-cell structure termed the virological synapse that is analogous to the immunological synapse (4). Subsequent studies revealed that HIV-1 could also be transmitted via virological synapses between CD4 ϩ T cells (5) and that infected cells could even form polysynapses, thereby allowing simultaneous cell-to-cell transmissions from a single infected cell to multiple uninfected target cells (6). Cell-to-cell transmission between infected macrophages and uninfected CD4ϩ T cells has also been described (7). Further, a less common mode of transmission between CD4 ϩ T cells was shown to exist in which HIV-1 can be transmitted by long membrane nanotubes that are formed after cell division (8). A vis...

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“…6 -10 Caveolin is thought to be necessary for caveolae formation and overexpression of caveolin can induce caveolae in cells that normally lack them. 11 Caveolin exists in three isoforms. [12][13][14] The first two isoforms, cav-1 and cav-2, are highly expressed in vascular endothelium, pericytes and smooth muscle, among other cell types, whereas cav-3 is confined to muscle.…”

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confidence: 99%

Vascular Permeability and Pathological Angiogenesis in Caveolin-1-Null Mice

Chang

Feng

Nagy

et al. 2009

The American Journal of Pathology

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Caveolin-1, the signature protein of endothelial cell caveolae, has many important functions in vascular cells. Caveolae are thought to be the transcellular pathway by which plasma proteins cross normal capillary endothelium, but, unexpectedly, cav-1 ؊/؊ mice, which lack caveolae, have increased permeability to plasma albumin. The acute increase in vascular permeability induced by agents such as vascular endothelial growth factor (VEGF)-A occurs through venules, not capillaries, and particularly through the vesiculo-vacuolar organelle (VVO), a unique structure composed of numerous interconnecting vesicles and vacuoles that together span the venular endothelium from lumen to ablumen. Furthermore, the hyperpermeable blood vessels found in pathological angiogenesis, mother vessels, are derived from venules. The present experiments made use of cav-1 ؊/؊ mice to investigate the relationship between caveolae and VVOs and the roles of caveolin-1 in VVO structure in the acute vascular hyperpermeability induced by VEGF-A and in pathological angiogenesis and associated chronic vascular hyperpermeability. We found that VVOs expressed caveolin-1 variably but, in contrast to caveolae, were present in normal numbers and with apparently unaltered structure in cav-1 ؊/؊ mice. Nonetheless, VEGF-A-induced hyperpermeability was strikingly reduced in cav-1 ؊/؊ mice, as was pathological angiogenesis and associated chronic vascular hyperpermeability, whether induced by VEGF-A 164 or by a tumor. Thus, caveolin-1 is not necessary for VVO structure but may have important roles in regulating VVO function in acute vascular hyperpermeability and angiogenesis. (Am J Pathol

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Expression of caveolin‐1 in lymphocytes induces caveolae formation and recruitment of phosphofructokinase to the plasma membrane

Cited by 25 publications

References 60 publications

Functional expression of sodium-glucose transporters in cancer

Functional expression of sodium-glucose transporters in cancer

Productive Entry of HIV-1 during Cell-to-Cell Transmission via Dynamin-Dependent Endocytosis

Vascular Permeability and Pathological Angiogenesis in Caveolin-1-Null Mice

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