C-terminal Loop 13 of Na+/Glucose Cotransporter 1 Contains Both Stereospecific and Non-stereospecific Sugar Interaction Sites

Wimmer, Barbara; Raja, Mobeen; Hinterdorfer, Peter; Gruber, Hermann J.; Kinne, Rolf

doi:10.1074/jbc.m805082200

Cited by 12 publications

(8 citation statements)

References 29 publications

(33 reference statements)

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“…Chinese hamster ovary cells stably expressing rbSGLT1 (CHO‐G6D3) generated in our laboratory [Lin et al, 1998] were used. We have used these cells as a model to study the intracellular mechanisms of biosynthesis and functional regulation of rbSGLT1 [Raja et al, 2004; Puntheeranurak et al, 2007; Wimmer et al, 2009]. CHO‐GD3 cells grown in 25 cm 2 flasks (Falcon, Heidelberg, Germany) under 7.5% CO 2 at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Protein kinase C mediated intracellular signaling pathways are involved in the regulation of sodium‐dependent glucose co‐transporter SGLT1 activity

Castaneda‐Sceppa

Subramanian

Castañeda

2010

J of Cellular Biochemistry

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The sodium-dependent glucose co-transporter (SGLT1) is regulated by protein kinases. The aim of the present study was to examine the role of protein kinase C (PKC) in the regulation of rabbit (rb) SGLT1 activity as determined by alpha-methyl-D-glucopyranoside (AMG) uptake and to identify the cellular mechanisms involved in this process. For this purpose Chinese hamster ovary cells expressing rbSGLT1 (CHO-G6D3) were treated with PKC activators and inhibitors. PKC activators did not exert any effect on AMG uptake, as corroborated by mutation of the putative phosphorylation sites of PKC. In contrast, the PKC inhibitor bisindolylmaleimide I (BIM) increased AMG uptake. This effect was associated with translocation of rbSGLT1 from the intracellular pool to the plasma membrane demonstrated by pre-treatment of G6D3 cells with cytochalasin D that abolished the effect of BIM. In addition, intracellular signaling pathways (p38/MAPK, ERK/MAPK, JNK/MAPK, and PI3K/Akt/mTOR) were associated with PKC-regulated AMG uptake. Moreover, rbSGLT1 mRNA level was higher in BIM-treated cells than in untreated, control cells. This effect was completely abolished by actinomycin D treatment. The present study demonstrates that PKC regulates rbSGLT1 activity via a complex intracellular mechanism that involves sorting and transcriptional regulation of rbSGLT1. The study findings suggest the involvement of two complementary opposite mechanism of action, in which the balance between two antagonistic effects, namely stimulation and inhibition of the transporter, regulates the activity of rbSGLT1 by PKC.

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Section: Methodsmentioning

confidence: 99%

Protein kinase C mediated intracellular signaling pathways are involved in the regulation of sodium‐dependent glucose co‐transporter SGLT1 activity

Castaneda‐Sceppa

Subramanian

Castañeda

2010

J of Cellular Biochemistry

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“…Since ThrE also utilizes L-Ser as a substrate, it would be interesting to test the consequences of ThrE deletion for Ser accumulation. An example of the stereospecificity of transporters is the rabbit Na ϩ /glucose cotransporter, which favors the recognition of D-glucose over that of L-glucose (41). Other examples relate to the specificity of drugs accepted by transporters, such as the proton-coupled folate transporter PCFT of Mammalia, which has 40-fold greater affinity for the folate analogue L-amethopterin than for D-amethopterin (25).…”

Section: Discussionmentioning

confidence: 99%

Corynebacterium glutamicum as a Host for Synthesis and Export of d -Amino Acids

et al. 2011

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A number of D-amino acids occur in nature, and there is growing interest in their function and metabolism, as well as in their production and use. Here we use the well-established L-amino-acid-producing bacterium Corynebacterium glutamicum to study whether D-amino acid synthesis is possible and whether mechanisms for the export of these amino acids exist. In contrast to Escherichia coli, C. glutamicum tolerates D-amino acids added extracellularly. Expression of argR (encoding the broad-substrate-specific racemase of Pseudomonas taetrolens) with its signal sequence deleted results in cytosolic localization of ArgR in C. glutamicum. The isolated enzyme has the highest activity with lysine (100%) but also exhibits activity with serine (2%). Upon overexpression of argR in an L-arginine, L-ornithine, or L-lysine producer, equimolar mixtures of the D-and L-enantiomers accumulated extracellularly. Unexpectedly, argR overexpression in an L-serine producer resulted in extracellular accumulation of a surplus of D-serine (81 mM D-serine and 37 mM L-serine) at intracellular concentrations of 125 mM D-serine plus 125 mM L-serine. This points to a nonlimiting ArgR activity for intracellular serine racemization and to the existence of a specific export carrier for D-serine. Export of D-lysine relies fully on the presence of lysE, encoding the exporter for L-lysine, which is apparently promiscuous with respect to the chirality of lysine. These data show that D-amino acids can also be produced with C. glutamicum and that in special cases, due to specific carriers, even a preferential extracellular accumulation of this enantiomer is possible.Corynebacterium glutamicum is well known for its extraordinary L-amino acid production properties. Its most prominent feature is probably its capacity to produce L-glutamate, 1.8 million tons of which are currently produced per year and used as a sodium salt to be added to food (24). Another amino acid made with C. glutamicum is L-lysine, which is required for animal nutrition. Indeed, over the years, C. glutamicum strains have been developed for the production of almost all the L-amino acids with commercial potential. For instance, our own group has contributed to the development of C. glutamicum strains producing L-isoleucine (7), L-valine (30), L-threonine (5), and L-serine (37).Obviously, given the success of amino acid production by C. glutamicum and other bacteria, and the fact that sugar is a renewable substrate, bacterial production of further compounds has great appeal. Processes to enable the production of succinate (28), lactate (29), cadaverine (14), putrescine (32), 2-oxoisovalerate (19), and isobutanol (35) by C. glutamicum have been described. D-Amino acids constitute another interesting group of products, although their direct biotechnological production by bacteria has not yet been investigated. A significant reason is probably that it is unclear whether the cell can tolerate the coexistence of D-and L-amino acids. In fact, the growth of Currently, D-amino acids are produced ...

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“…To this end various methods have been used such as kinetic studies (7), electrophysiology methods (8), tryptophan scanning studies (9,10), mutagenesis studies (11,12), x-ray crystallography (13), and plasmon resonance spectroscopy (14) to name a few. Crystallographic data are available for Vibrio parahemeolyticus sodium/galactose symporter (vSGLT) (13) in the sodium-and galactose-bound state.…”

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confidence: 99%

“…The extracellular location and * This work was supported by the State of Upper Austria and the Austrian accessibility of three extramembraneous loops (loop 6 -7, loop 8 -9, and loop [13][14] was identified. They form a vestibule for the entry of the sugar into the translocation pathway and contain the first of several sugar recognition sites.…”

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confidence: 99%

Forces and Dynamics of Glucose and Inhibitor Binding to Sodium Glucose Co-transporter SGLT1 Studied by Single Molecule Force Spectroscopy

Neundlinger

Puntheeranurak

Wildling

et al. 2014

Journal of Biological Chemistry

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Background: SGLT1 functions in intestinal glucose absorption and renal reabsorption. Results: With increasing temperature, width of energy barrier and average life time increased for glucose binding to SGLT1 but decreased for phlorizin binding. Conclusion: Sugar translocation and inhibitor binding involves several steps with different temperature sensitivity. Significance: Force spectroscopy can be used to study dynamics and structure of membrane transporter.

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C-terminal Loop 13 of Na+/Glucose Cotransporter 1 Contains Both Stereospecific and Non-stereospecific Sugar Interaction Sites

Cited by 12 publications

References 29 publications

Protein kinase C mediated intracellular signaling pathways are involved in the regulation of sodium‐dependent glucose co‐transporter SGLT1 activity

Protein kinase C mediated intracellular signaling pathways are involved in the regulation of sodium‐dependent glucose co‐transporter SGLT1 activity

Corynebacterium glutamicum as a Host for Synthesis and Export of d -Amino Acids

Forces and Dynamics of Glucose and Inhibitor Binding to Sodium Glucose Co-transporter SGLT1 Studied by Single Molecule Force Spectroscopy

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