Structure/functional aspects of the human riboflavin transporter-3 (<i>SLC52A3</i>): role of the predicted glycosylation and substrate-interacting sites

Subramanian, Veedamali S.; Sabui, Subrata; Teafatiller, Trevor; Bohl, Jennifer A.; Said, Hamid M.

doi:10.1152/ajpcell.00101.2017

Cited by 13 publications

(11 citation statements)

References 48 publications

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“…C20orf54 (SLC52A3) encodes a plasma membrane transporter mediating the uptake of vitamin B2/riboflavin that is vital in biochemical oxidation–reduction reactions [ 36 ]. The mutation of SLC52A3 may cause degenerative disorders like Brown-Vialetto-Van-Laere syndrome (BVVL) [ 37 ] and Amyotrophic lateral sclerosis (ALS) [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of contributing genes of Huntington’s disease by machine learning

et al. 2020

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Background Huntington’s disease (HD) is an inherited disorder caused by the polyglutamine (poly-Q) mutations of the HTT gene results in neurodegeneration characterized by chorea, loss of coordination, cognitive decline. However, HD pathogenesis is still elusive. Despite the availability of a wide range of biological data, a comprehensive understanding of HD’s mechanism from machine learning is so far unrealized, majorly due to the lack of needed data density. Methods To harness the knowledge of the HD pathogenesis from the expression profiles of postmortem prefrontal cortex samples of 157 HD and 157 controls, we used gene profiling ranking as the criteria to reduce the dimension to the order of magnitude of the sample size, followed by machine learning using the decision tree, rule induction, random forest, and generalized linear model. Results These four Machine learning models identified 66 potential HD-contributing genes, with the cross-validated accuracy of 90.79 ± 4.57%, 89.49 ± 5.20%, 90.45 ± 4.24%, and 97.46 ± 3.26%, respectively. The identified genes enriched the gene ontology of transcriptional regulation, inflammatory response, neuron projection, and the cytoskeleton. Moreover, three genes in the cognitive, sensory, and perceptual systems were also identified. Conclusions The mutant HTT may interfere with both the expression and transport of these identified genes to promote the HD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Identification of contributing genes of Huntington’s disease by machine learning

et al. 2020

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“…In both latter cases, the effects were found to be mediated, at least in part, via transcriptional mechanism(s) involving the SLC52A3 gene (1,36). Other investigations from our laboratory have delineated certain cell biological aspects of the hRFVT-3 system that are relevant to its targeting to the apical membrane domain of the absorptive epithelia and to its intracellular trafficking (37,41). So far, however, it is not known whether the intestinal RFVT-3 system has interacting protein(s) and, if so, what effect(s) such interaction(s) has on its function and/or cell biology.…”

Section: Introductionmentioning

confidence: 87%

Identification of transmembrane protein 237 as a novel interactor with the intestinal riboflavin transporter-3 (RFVT-3): role in functionality and cell biology

Sabui

Subramanian

Pham

et al. 2019

American Journal of Physiology-Cell Physiology

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The apically localized riboflavin (RF) transporter-3 (RFVT-3) is involved in intestinal absorption of vitamin B2. Previous studies have characterized different physiological/biological aspects of the RFVT-3, but there is a lack of knowledge regarding possible existence of interacting partner(s) and consequence of interaction(s) on its function/cell biology. To address the latter, we performed yeast two-hybrid (Y2H) screening of a human colonic cDNA library and have identified transmembrane protein 237 (TMEM237) as a putative interactor with the human (h)RFVT-3; the interaction was further confirmed via “1-by-1” Y2H assay that involved appropriate positive and negative controls. TMEM237 was found to be highly expressed in human native intestine and in human intestinal epithelial cell lines; further, confocal images showed colocalization of the protein with hRFVT-3. The interaction between TMEM237 with hRFVT-3 in human intestinal epithelial HuTu-80 cells was established by coimmunoprecipitation. Expressing TMEM237 in HuTu-80 cells led to a significant induction in RF uptake, while its knockdown (with the use of gene-specific siRNA) led to a significant reduction in uptake. Transfecting TMEM237 into HuTu-80 cells also led to a marked enhancement in hRFVT-3 protein stability (reflected by an increase in the protein half-life). Interestingly, the level of expression of TMEM237 was found to be markedly reduced following treatment with TNF-α (a proinflammatory cytokine that inhibits intestinal RF uptake), while its expression was significantly upregulated following treatment with butyrate (an inducer of intestinal RF uptake). These findings identify TMEM237 as an interactor with the intestinal hRFVT-3 and show that the interaction has physiological/biological significance.

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“…Caco-2 cells and mouse colonoids treated with NaB and controls were lysed in 1X protease cocktail inhibitor mixture (Roche, Indianapolis, IN) containing RIPA buffer (Sigma) and the total protein was prepared as described [45, 46]. Sixty micrograms of total protein was loaded on 4–12% premade mini gels (Invitrogen) and protein was transferred to polyvinylidene difluoride (PVDF) membranes.…”

Section: Methodsmentioning

confidence: 99%

“…After transfer the membranes were blocked in Odyssey blocking buffer (LI-COR) and then probed either with hRFVT3 (1:200 dilution) (custom antibody generated by Alpha diagnostic, San Antonio, TX) or mRFVT3 (1:500 dilution) (Biosis Antibodies, Woburn, MA) and β-actin (Santa Cruz Biotechnology) polyclonal antibodies. The specificity of both the antibodies were established before using variety of cell lysates [27, 45, 46]. The membranes were washed then probed with corresponding secondary antibodies (LICOR Biosciences) in 1:30,000 dilutions for 1 hr at room temperature and the specific bands were quantified using Odyssey application software supplied in an Odyssey Infrared imaging system (LI-COR Biosciences).…”

Section: Methodsmentioning

confidence: 99%

Sodium Butyrate Enhances Intestinal Riboflavin Uptake via Induction of Expression of Riboflavin Transporter-3 (RFVT3)

et al. 2018

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Background: Uptake of riboflavin (RF) by intestinal epithelial cells occurs via a specific carrier-mediated process that involves the apically localized RF transporter-3 (RFVT3). Previous studies have shown that sodium butyrate (NaB) affects intestinal uptake of other substrates and expression of their membrane transporters, but its effect on intestinal uptake of RF and expression of RFVT3 has not been examined. Aims: To investigate the effect of NaB on intestinal RF uptake process and expression of the RFVT3. Methods: Two experimental models were used in this study: Human-derived intestinal epithelial Caco-2 cells and ex vivo mouse colonoids. 3H-RF uptake assay, western blot, RT-qPCR and chromatin immunoprecipitation (ChIP) assay were performed. Results: Treating Caco-2 cells with NaB led to a significant increase in carrier-mediated RF uptake. This increase was associated with a significant induction in the level of expression of the hRFVT3 protein, mRNA and heterogenous nuclear RNA (hnRNA) Similarly, treating mouse colonoids with NaB led to a marked increase in the level of expression of the mRFVT3 protein, mRNA and hnRNA. NaB did not affect hRFVT3 mRNA stability, rather it caused significant epigenetic changes (histone modifications) in the SLC52A3 gene where an increase in H3Ac and a reduction in H3K27me3 levels were observed in the NaB treated Caco-2 cells compared to untreated controls. Conclusion: These findings demonstrate that NaB up-regulates intestinal RF uptake and that the effect appears to be mediated, at least in part, at the level of transcription of the SLC52A3 gene and may involve epigenetic mechanism(s).

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Structure/functional aspects of the human riboflavin transporter-3 (SLC52A3): role of the predicted glycosylation and substrate-interacting sites

Cited by 13 publications

References 48 publications

Identification of contributing genes of Huntington’s disease by machine learning

Identification of contributing genes of Huntington’s disease by machine learning

Identification of transmembrane protein 237 as a novel interactor with the intestinal riboflavin transporter-3 (RFVT-3): role in functionality and cell biology

Sodium Butyrate Enhances Intestinal Riboflavin Uptake via Induction of Expression of Riboflavin Transporter-3 (RFVT3)

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