Proteasomal Modulation of Cellular SNAT2 (SLC38A2) Abundance and Function by Unsaturated Fatty Acid Availability

Nardi, Francesca; Hoffmann, Thorsten M.; Stretton, Clare; Cwiklinski, Emma; Taylor, Peter M.; Hundal, Harinder S.

doi:10.1074/jbc.m114.625137

Cited by 35 publications

(39 citation statements)

References 38 publications

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“…A recent study has suggested that proteasomal degradation explains decreased SNAT2 induction by unsaturated fatty acids under stress conditions (31). Inhibition of the proteasome caused the accumulation of immature SNAT2 but not the fully glycosylated transporter (31). In our experiments, decreased SNAT2 protein caused by Sal was not due to proteasomal degradation.…”

Section: Discussionsupporting

confidence: 58%

“…It has been reported that turnover of the SNAT2 protein depends on the ubiquitin proteasome system via the involvement of the ubiquitin E3 ligase NEDD4-2 (44). A recent study has suggested that proteasomal degradation explains decreased SNAT2 induction by unsaturated fatty acids under stress conditions (31). Inhibition of the proteasome caused the accumulation of immature SNAT2 but not the fully glycosylated transporter (31).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported previously that the role of SNAT2 in the adaptation to amino acid starvation can be decreased by the presence of unsaturated fatty acids (31). This mechanism involved proteasomal degradation of the partially processed SNAT2 protein.…”

Section: Gadd34 Is Induced During Hyperosmotic Stress In An Atf4mentioning

confidence: 99%

“…Membrane fractions were obtained as described previously (31). Biotinylated plasma membrane proteins were isolated with a cell surface protein isolation kit (Pierce) according to the instructions of the manufacturer.…”

Section: Methodsmentioning

confidence: 99%

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Coordinated Regulation of the Neutral Amino Acid Transporter SNAT2 and the Protein Phosphatase Subunit GADD34 Promotes Adaptation to Increased Extracellular Osmolarity

Krokowski

Jobava

Guan

et al. 2015

Journal of Biological Chemistry

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Background: Increased phosphorylation of the translation initiation factor eIF2␣ (eIF2␣-P) promotes apoptosis during hyperosmotic stress. Results: Induction of the PP1 phosphatase subunit GADD34 (which dephosphorylates eIF2␣-P) promotes adaptation. Conclusion: GADD34 promotes survival by increasing the uptake of small neutral amino acids via the amino acid transporter SNAT2. Significance: Rapid adaptation to changes in extracellular osmolarity is inhibited by eIF2␣-P signaling.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Gadd34 Is Induced During Hyperosmotic Stress In An Atf4mentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Coordinated Regulation of the Neutral Amino Acid Transporter SNAT2 and the Protein Phosphatase Subunit GADD34 Promotes Adaptation to Increased Extracellular Osmolarity

Krokowski

Jobava

Guan

et al. 2015

Journal of Biological Chemistry

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“…Finally, another amino acid transporter, system A/SNAT2 (SLC38A2), is regulated differentially at the transcriptional and post-translational levels. Amino acid starvation and hypertonicity increase SNAT2 mRNA; however, stress conditions promote the proteasome-dependent degradation of SNAT2 39, 40 . It is possible that LAT1 in beta cells could be differentially regulated at the transcriptional and post-translational level in a similar manner, with nutrient availability and/or signaling determining the trafficking or degradation of LAT1 protein.…”

Section: Discussionmentioning

confidence: 99%

Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas

et al. 2016

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Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2- 18F-fluoroethoxy)-L-tryptophan ( 18F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of 18F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodistribution. Both dynamic and static positron emission tomography (PET) images were acquired in wild-type and Akita mice, a model of ER stress-induced diabetes, as well as in mice treated with streptozotocin (STZ). LAT1 expression in both groups of mice was evaluated by immunofluorescence microscopy. Results: Uptake of 18F-L-FEHTP was highest in the pancreas, and static PET images showed highly specific pancreatic signal. Time-activity curves showed significantly reduced 18F-L-FEHTP uptake in Akita mice, and LAT1 expression was also reduced. However, mice treated with STZ, in which beta cell mass was reduced by 62%, showed no differences in 18F-L-FEHTP uptake in the pancreas, and there was no significant correlation of 18F-L-FEHTP uptake with beta cell mass. Conclusions: 18F-L-FEHTP is highly specific for the pancreas with little background uptake in kidney or liver. We were able to detect changes in LAT1 in a mouse model of diabetes, but these changes did not correlate with beta cell function or mass. Therefore, 18F-L-FEHTP PET is not a suitable method for the noninvasive imaging of changes in beta cell function during the progression of diabetes.

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Lipid modulation of skeletal muscle mass and function

Lipina

Hundal

2016

J cachexia sarcopenia muscle

178

156

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Loss of skeletal muscle mass is a characteristic feature of various pathologies including cancer, diabetes, and obesity, as well as being a general feature of ageing. However, the processes underlying its pathogenesis are not fully understood and may involve multiple factors. Importantly, there is growing evidence which supports a role for fatty acids and their derived lipid intermediates in the regulation of skeletal muscle mass and function. In this review, we discuss evidence pertaining to those pathways which are involved in the reduction, increase and/or preservation of skeletal muscle mass by such lipids under various pathological conditions, and highlight studies investigating how these processes may be influenced by dietary supplementation as well as genetic and/or pharmacological intervention.

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Proteasomal Modulation of Cellular SNAT2 (SLC38A2) Abundance and Function by Unsaturated Fatty Acid Availability

Cited by 35 publications

References 38 publications

Coordinated Regulation of the Neutral Amino Acid Transporter SNAT2 and the Protein Phosphatase Subunit GADD34 Promotes Adaptation to Increased Extracellular Osmolarity

Coordinated Regulation of the Neutral Amino Acid Transporter SNAT2 and the Protein Phosphatase Subunit GADD34 Promotes Adaptation to Increased Extracellular Osmolarity

Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas

Lipid modulation of skeletal muscle mass and function

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