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Article: Betaine chemistry, roles, and potential use in liver disease.

Day, Christopher R / Kempson, Stephen A

2016 Volume 1860, Issue 6, Page(s) 1098–1106

Abstract: Background: Betaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is utilized in the kidney primarily as an osmoprotectant, whereas in the liver ...

Abstract	Background: Betaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is utilized in the kidney primarily as an osmoprotectant, whereas in the liver its primary role is in metabolism as a methyl group donor. In both organs, a specific betaine transporter mediates cellular uptake of betaine from plasma. The abundance of both betaine and the betaine transporter in liver greatly exceeds that of other organs. Scope of review: The remarkable contributions of betaine to normal human and animal health are summarized together with a discussion of the mechanisms and potential beneficial effects of dietary betaine supplements on liver disease. Major conclusions: A significant amount of data from animal models of liver disease indicates that administration of betaine can halt and even reverse progression of the disruption of liver function. Betaine is well-tolerated, inexpensive, effective over a wide range of doses, and is already used in livestock feeding practices. General significance: The accumulated data indicate that carefully controlled additional investigations in humans are merited. The focus should be on the long-term use of betaine in large patient populations with liver diseases characterized by development of fatty liver, especially non-alcoholic fatty liver disease and alcoholic liver disease.
MeSH term(s)	Animals ; Betaine/chemistry ; Betaine/metabolism ; Betaine/therapeutic use ; Humans ; Kidney/metabolism ; Liver/metabolism ; Liver Diseases/drug therapy ; Liver Diseases, Alcoholic/drug therapy ; Non-alcoholic Fatty Liver Disease/drug therapy
Chemical Substances	Betaine (3SCV180C9W)
Language	English
Publishing date	2016-06
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbagen.2016.02.001
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Article: The betaine/GABA transporter and betaine: roles in brain, kidney, and liver.

Kempson, Stephen A / Zhou, Yun / Danbolt, Niels C

Frontiers in physiology

2014 Volume 5, Page(s) 159

Abstract: The physiological roles of the betaine/GABA transporter (BGT1; slc6a12) are still being debated. BGT1 is a member of the solute carrier family 6 (the neurotransmitter, sodium symporter transporter family) and mediates cellular uptake of betaine and GABA ... ...

Abstract	The physiological roles of the betaine/GABA transporter (BGT1; slc6a12) are still being debated. BGT1 is a member of the solute carrier family 6 (the neurotransmitter, sodium symporter transporter family) and mediates cellular uptake of betaine and GABA in a sodium- and chloride-dependent process. Most of the studies of BGT1 concern its function and regulation in the kidney medulla where its role is best understood. The conditions here are hostile due to hyperosmolarity and significant concentrations of NH4Cl and urea. To withstand the hyperosmolarity, cells trigger osmotic adaptation, involving concentration of a transcriptional factor TonEBP/NFAT5 in the nucleus, and accumulate betaine and other osmolytes. Data from renal cells in culture, primarily MDCK, revealed that transcriptional regulation of BGT1 by TonEBP/NFAT5 is relatively slow. To allow more acute control of the abundance of BGT1 protein in the plasma membrane, there is also post-translation regulation of BGT1 protein trafficking which is dependent on intracellular calcium and ATP. Further, betaine may be important in liver metabolism as a methyl donor. In fact, in the mouse the liver is the organ with the highest content of BGT1. Hepatocytes express high levels of both BGT1 and the only enzyme that can metabolize betaine, namely betaine:homocysteine -S-methyltransferase (BHMT1). The BHMT1 enzyme removes a methyl group from betaine and transfers it to homocysteine, a potential risk factor for cardiovascular disease. Finally, BGT1 has been proposed to play a role in controlling brain excitability and thereby represents a target for anticonvulsive drug development. The latter hypothesis is controversial due to very low expression levels of BGT1 relative to other GABA transporters in brain, and also the primary location of BGT1 at the surface of the brain in the leptomeninges. These issues are discussed in detail.
Language	English
Publishing date	2014-04-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2014.00159
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Article ; Online: Betaine transport in kidney and liver: use of betaine in liver injury.

Kempson, Stephen A / Vovor-Dassu, Komi / Day, Christopher

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

2013 Volume 32, Issue 7, Page(s) 32–40

Abstract: Betaine, also known as trimethylglycine, is an important human nutrient obtained from a variety of foods and also can be synthesized from choline. Betaine is much more abundant in kidney and liver compared to other mammalian organs. The principal role of ...

Abstract	Betaine, also known as trimethylglycine, is an important human nutrient obtained from a variety of foods and also can be synthesized from choline. Betaine is much more abundant in kidney and liver compared to other mammalian organs. The principal role of betaine in the kidney is osmoprotection in cells of the medulla and it enters these cells via the betaine/γ-aminobutyric acid (GABA) transporter protein (BGT1), which is upregulated by hyperosmotic stress. This process has been studied in great detail. In liver, the main role of betaine is a methyl donor in the methionine cycle. However, recent studies showed that BGT1 is much more abundant in liver compared to kidney medulla. Despite this, the role of BGT1 in liver has received little attention. Entry of betaine into liver cells is a necessary first step for its action at the cellular level. Increased interest in betaine has developed because of a number of therapeutic uses. These include treatment of nonalcoholic fatty liver and hyperhomocysteinemia, a risk factor for atherosclerotic disease. Several important questions need to be addressed to better understand the potential of betaine as a therapeutic agent for other liver diseases, such as alcohol-induced injury. Heavy alcohol consumption is the most common cause for liver-related deaths and altered liver metabolism may contribute to hepatic, vascular, coronary, and cerebral diseases.
MeSH term(s)	Alcohol Drinking/drug therapy ; Alcohol Drinking/metabolism ; Alcohol Drinking/pathology ; Betaine/metabolism ; Betaine/therapeutic use ; Biological Transport ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; GABA Plasma Membrane Transport Proteins/metabolism ; Hepatocytes/metabolism ; Humans ; Kidney/drug effects ; Kidney/metabolism ; Kidney Medulla/drug effects ; Kidney Medulla/metabolism ; Liver/drug effects ; Liver/injuries ; Liver/metabolism
Chemical Substances	Carrier Proteins ; GABA Plasma Membrane Transport Proteins ; betaine plasma membrane transport proteins (146313-33-9) ; Betaine (3SCV180C9W)
Language	English
Publishing date	2013-12-18
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1067572-3
ISSN	1421-9778 ; 1015-8987
ISSN (online)	1421-9778
ISSN	1015-8987
DOI	10.1159/000356622
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Article: Betaine chemistry, roles, and potential use in liver disease

Day, Christopher R / Stephen A. Kempson

Biochimica et biophysica acta. 2016 June, v. 1860, no. 6

2016

Abstract: Betaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is utilized in the kidney primarily as an osmoprotectant, whereas in the liver its primary ... ...

Abstract	Betaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is utilized in the kidney primarily as an osmoprotectant, whereas in the liver its primary role is in metabolism as a methyl group donor. In both organs, a specific betaine transporter mediates cellular uptake of betaine from plasma. The abundance of both betaine and the betaine transporter in liver greatly exceeds that of other organs.The remarkable contributions of betaine to normal human and animal health are summarized together with a discussion of the mechanisms and potential beneficial effects of dietary betaine supplements on liver disease.A significant amount of data from animal models of liver disease indicates that administration of betaine can halt and even reverse progression of the disruption of liver function. Betaine is well-tolerated, inexpensive, effective over a wide range of doses, and is already used in livestock feeding practices.The accumulated data indicate that carefully controlled additional investigations in humans are merited. The focus should be on the long-term use of betaine in large patient populations with liver diseases characterized by development of fatty liver, especially non-alcoholic fatty liver disease and alcoholic liver disease.
Keywords	animal models ; betaine ; chemistry ; fatty liver ; food intake ; glycine (amino acid) ; humans ; kidneys ; liver ; liver function ; livestock feeding ; metabolism ; osmotolerance ; patients
Language	English
Dates of publication	2016-06
Size	p. 1098-1106.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	840755-1
ISSN	0304-4165
ISSN	0304-4165
DOI	10.1016/j.bbagen.2016.02.001
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Mutation of a single threonine in the cytoplasmic NH2 terminus disrupts trafficking of renal betaine-GABA transporter 1 during hypertonic stress.

Schweikhard, Eva S / Kempson, Stephen A / Ziegler, Christine / Burckhardt, Birgitta C

American journal of physiology. Renal physiology

2014 Volume 307, Issue 1, Page(s) F107–15

Abstract: Betaine is an important osmolyte and is, compared with other organs, much more abundant in the kidneys, where it enters cells in the medulla by betaine-GABA transporter 1 (BGT1) to balance osmoregulation in the countercurrent system. In wild-type (wt-) ... ...

Abstract	Betaine is an important osmolyte and is, compared with other organs, much more abundant in the kidneys, where it enters cells in the medulla by betaine-GABA transporter 1 (BGT1) to balance osmoregulation in the countercurrent system. In wild-type (wt-)BGT1-expressing oocytes, GABA-mediated currents were diminished by preincubation of oocytes with 100 nM PMA or 5 μM dioctanoyl-sn-glycerol, activators of PKC, whereas the application of staurosporine before the application of dioctanoyl-sn-glycerol restored the response to GABA. Four potential phosphorylation sites on BGT1 were mutated to alanine by site-directed mutagenesis. Three mutants (T235A, S428A, and S564A) evoked GABA currents comparable in magnitude to currents observed in wt-BGT1-expressing oocytes, whereas GABA currents in T40A were barely detectable. Uptake of [(3)H]GABA was also determined in human embryonic kidney-293 cells expressing enhanced green fluorescent protein (EGFP)-tagged BGT1 with the same mutations. T235A, S428A, and S564A showed upregulation of GABA uptake after hypertonic stress and downregulation by PMA similar to EGFP-wt-BGT1. In contrast, T40A did not respond to either hypertonicity or PMA. Confocal microscopy of the EGFP-BGT1 mutants expressed in Madin-Darby canine kidney cells revealed that T40A was present in the cytoplasm after 24 h of hypertonic stress. whereas the other mutants and EGFP-wt-BGT1 were in the plasma membrane. All mutants, including T40A, comigrated with wt-BGT1 on Western blots, suggesting that they are full-length proteins. T40A, however, cannot be phosphorylated, as revealed using a specific anti-phosphoantibody, and, therefore, T40 may be important for the trafficking and insertion of BGT1 in the plasma membrane.
MeSH term(s)	Animals ; Betaine/pharmacology ; Cell Line ; GABA Plasma Membrane Transport Proteins/genetics ; Humans ; Kidney/metabolism ; Mutagenesis, Site-Directed/methods ; Mutation/genetics ; Osmotic Pressure/drug effects ; Osmotic Pressure/physiology ; Protein Transport/physiology ; Threonine/genetics ; Threonine/metabolism ; Transcriptional Activation/drug effects ; Transcriptional Activation/genetics ; Xenopus
Chemical Substances	GABA Plasma Membrane Transport Proteins ; Threonine (2ZD004190S) ; Betaine (3SCV180C9W)
Language	English
Publishing date	2014-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00085.2014
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Article ; Online: Betaine Transport in Kidney and Liver: Use of Betaine in Liver Injury

Kempson, Stephen A. / Vovor-Dassu, Komi / Day, Christopher

Cellular Physiology and Biochemistry - International Journal of Experimental Cellular Physiology, Biochemistry and Pharmacology

2013 Volume 32, Issue S1, Page(s) 32–40

Abstract	Betaine, also known as trimethylglycine, is an important human nutrient obtained from a variety of foods and also can be synthesized from choline. Betaine is much more abundant in kidney and liver compared to other mammalian organs. The principal role of betaine in the kidney is osmoprotection in cells of the medulla and it enters these cells via the betaine/γ-aminobutyric acid (GABA) transporter protein (BGT1), which is upregulated by hyperosmotic stress. This process has been studied in great detail. In liver, the main role of betaine is a methyl donor in the methionine cycle. However, recent studies showed that BGT1 is much more abundant in liver compared to kidney medulla. Despite this, the role of BGT1 in liver has received little attention. Entry of betaine into liver cells is a necessary first step for its action at the cellular level. Increased interest in betaine has developed because of a number of therapeutic uses. These include treatment of nonalcoholic fatty liver and hyperhomocysteinemia, a risk factor for atherosclerotic disease. Several important questions need to be addressed to better understand the potential of betaine as a therapeutic agent for other liver diseases, such as alcohol-induced injury. Heavy alcohol consumption is the most common cause for liver-related deaths and altered liver metabolism may contribute to hepatic, vascular, coronary, and cerebral diseases.© 2014 S. Karger AG, Basel
Keywords	Betaine/GABA transporter ; Alcohol ; Methyl donor ; Hepatocyte ; MDCK
Language	English
Publisher	S. Karger AG
Publishing place	Basel
Publishing country	Switzerland
Document type	Article ; Online
ISSN	1421-9778 ; 1015-8987 ; 1015-8987
ISSN (online)	1421-9778
ISSN	1015-8987
DOI	10.1159/000356622
Database	Karger publisher's database

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Article: Betaine Transport in Kidney and Liver: Use of Betaine in Liver Injury

Kempson, Stephen A. / Vovor-Dassu, Komi / Day, Christopher

Cellular Physiology and Biochemistry

2013 Volume 32, Issue 1, Page(s) 32–40

Institution	Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
Abstract	Betaine, also known as trimethylglycine, is an important human nutrient obtained from a variety of foods and also can be synthesized from choline. Betaine is much more abundant in kidney and liver compared to other mammalian organs. The principal role of betaine in the kidney is osmoprotection in cells of the medulla and it enters these cells via the betaine/γ-aminobutyric acid (GABA) transporter protein (BGT1), which is upregulated by hyperosmotic stress. This process has been studied in great detail. In liver, the main role of betaine is a methyl donor in the methionine cycle. However, recent studies showed that BGT1 is much more abundant in liver compared to kidney medulla. Despite this, the role of BGT1 in liver has received little attention. Entry of betaine into liver cells is a necessary first step for its action at the cellular level. Increased interest in betaine has developed because of a number of therapeutic uses. These include treatment of nonalcoholic fatty liver and hyperhomocysteinemia, a risk factor for atherosclerotic disease. Several important questions need to be addressed to better understand the potential of betaine as a therapeutic agent for other liver diseases, such as alcohol-induced injury. Heavy alcohol consumption is the most common cause for liver-related deaths and altered liver metabolism may contribute to hepatic, vascular, coronary, and cerebral diseases.
Keywords	Betaine/GABA transporter ; Alcohol ; Methyl donor ; Hepatocyte ; MDCK
Language	English
Publishing date	2013-12-18
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
ZDB-ID	1067572-3
ISBN	978-3-318-05402-6 ; 3-318-05402-X
ISSN	1421-9778 ; 1015-8987
ISSN (online)	1421-9778
ISSN	1015-8987
DOI	10.1159/000356622
Database	Karger publisher's database

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Article: Osmotic regulation of renal betaine transport: transcription and beyond.

Kempson, Stephen A / Montrose, Marshall H

Pflugers Archiv : European journal of physiology

2004 Volume 449, Issue 3, Page(s) 227–234

Abstract: Cells in the kidney inner medulla are routinely exposed to high extracellular osmolarity during normal operation of the urinary concentrating mechanism. One adaptation critical for survival in this environment is the intracellular accumulation of organic ...

Abstract	Cells in the kidney inner medulla are routinely exposed to high extracellular osmolarity during normal operation of the urinary concentrating mechanism. One adaptation critical for survival in this environment is the intracellular accumulation of organic osmolytes to balance the osmotic stress. Betaine is an important osmolyte that is accumulated via the betaine/gamma-aminobutyric acid transporter (BGT1) in the basolateral plasma membrane of medullary epithelial cells. In response to hypertonic stress, there is transcriptional activation of the BGT1 gene, followed by trafficking and membrane insertion of BGT1 protein. Transcriptional activation, triggered by changes in ionic strength and water content, is an early response that is a key regulatory step and has been studied in detail. Recent studies suggest there are additional post-transcriptional regulatory steps in the pathway leading to upregulation of BGT1 transport, and that additional proteins are required for membrane insertion. Reversal of this adaptive process, upon removal of hypertonic stress, involves a rapid efflux of betaine through specific release pathways, a reduction in betaine influx, and a slower downregulation of BGT1 protein abundance. There is much more to be learned about many of these steps in BGT1 regulation.
MeSH term(s)	Animals ; Betaine/metabolism ; Carrier Proteins/metabolism ; Gene Expression Regulation/physiology ; Humans ; Kidney/physiology ; Protein Transport/physiology ; Transcriptional Activation/physiology ; Water-Electrolyte Balance/physiology
Chemical Substances	Carrier Proteins ; betaine plasma membrane transport proteins (146313-33-9) ; Betaine (3SCV180C9W)
Language	English
Publishing date	2004-12
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-004-1338-6
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Article: Hypertonic upregulation of betaine transport in renal cells is blocked by a proteasome inhibitor.

Lammers, Philip E / Beck, Jeffrey A / Chu, Shaoyou / Kempson, Stephen A

Cell biochemistry and function

2005 Volume 23, Issue 5, Page(s) 315–324

Abstract: The renal betaine transporter (BGT1) protects cells in the hypertonic medulla by mediating uptake and accumulation of the osmolyte betaine. Transcription plays an essential role in upregulating BGT1 transport in MDCK cells subjected to hypertonic stress. ...

Abstract	The renal betaine transporter (BGT1) protects cells in the hypertonic medulla by mediating uptake and accumulation of the osmolyte betaine. Transcription plays an essential role in upregulating BGT1 transport in MDCK cells subjected to hypertonic stress. During hypertonic stress, the abundance of the transcription factor TonEBP increases and it shifts from the cytoplasm to the nucleus where it activates transcription of the BGT1 gene. Little is known about post-transcriptional regulation of BGT1 protein. In the presence of the proteasome inhibitor MG-132, which blocked nuclear translocation of TonEBP, the hypertonic upregulation of BGT1 protein and transport was prevented and cell viability in hypertonic medium was impaired over 24 h. Urea also prevented the hypertonic upregulation of BGT1 protein and transport, but did not interfere with TonEBP translocation and cell viability. Shorter treatments of hypertonic cells with MG-132 avoided viability problems and produced dose-dependent inhibition of translocation and transport. When stably transfected MDCK cells that over-expressed BGT1 were treated for 6 h with hypertonic medium containing 3 microM MG-132, there was 43% inhibition of nuclear translocation, 83% inhibition of BGT1 transport, and no change in viability. While other proteasome functions may be involved, these data are consistent with a critical role for nuclear translocation of TonEBP in upregulation and membrane insertion of BGT1 protein.
MeSH term(s)	Animals ; Betaine/metabolism ; Biological Transport/drug effects ; Carrier Proteins/antagonists & inhibitors ; Carrier Proteins/metabolism ; Cell Line ; Cell Nucleus/metabolism ; Cell Survival ; Cysteine Proteinase Inhibitors/pharmacology ; Cytoplasm/metabolism ; Dogs ; Dose-Response Relationship, Drug ; Hypertonic Solutions/pharmacology ; Isotonic Solutions/pharmacology ; Kidney/cytology ; Kidney/drug effects ; Kidney/metabolism ; Leupeptins/pharmacology ; gamma-Aminobutyric Acid/metabolism
Chemical Substances	Carrier Proteins ; Cysteine Proteinase Inhibitors ; Hypertonic Solutions ; Isotonic Solutions ; Leupeptins ; betaine plasma membrane transport proteins (146313-33-9) ; Betaine (3SCV180C9W) ; gamma-Aminobutyric Acid (56-12-2) ; benzyloxycarbonylleucyl-leucyl-leucine aldehyde (RF1P63GW3K)
Language	English
Publishing date	2005-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	283643-9
ISSN	1099-0844 ; 0263-6484
ISSN (online)	1099-0844
ISSN	0263-6484
DOI	10.1002/cbf.1241
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Article ; Online: Role of N-glycosylation in renal betaine transport.

Schweikhard, Eva S / Burckhardt, Birgitta C / Joos, Friedericke / Fenollar-Ferrer, Cristina / Forrest, Lucy R / Kempson, Stephen A / Ziegler, Christine

The Biochemical journal

2015 Volume 470, Issue 2, Page(s) 169–179

Abstract: The osmolyte and folding chaperone betaine is transported by the renal Na(+)-coupled GABA (γ-aminobutyric acid) symporter BGT-1 (betaine/GABA transporter 1), a member of the SLC6 (solute carrier 6) family. Under hypertonic conditions, the transcription, ... ...

Abstract	The osmolyte and folding chaperone betaine is transported by the renal Na(+)-coupled GABA (γ-aminobutyric acid) symporter BGT-1 (betaine/GABA transporter 1), a member of the SLC6 (solute carrier 6) family. Under hypertonic conditions, the transcription, translation and plasma membrane (PM) insertion of BGT-1 in kidney cells are significantly increased, resulting in elevated betaine and GABA transport. Re-establishing isotonicity involves PM depletion of BGT-1. The molecular mechanism of the regulated PM insertion of BGT-1 during changes in osmotic stress is unknown. In the present study, we reveal a link between regulated PM insertion and N-glycosylation. Based on homology modelling, we identified two sites (Asn(171) and Asn(183)) in the extracellular loop 2 (EL2) of BGT-1, which were investigated with respect to trafficking, insertion and transport by immunogold-labelling, electron microscopy (EM), mutagenesis and two-electrode voltage clamp measurements in Xenopus laevis oocytes and uptake of radiolabelled substrate into MDCK (Madin-Darby canine kidney) and HEK293 (human embryonic kidney) cells. Trafficking and PM insertion of BGT-1 was clearly promoted by N-glycosylation in both oocytes and MDCK cells. Moreover, association with N-glycans at Asn(171) and Asn(183) contributed equally to protein activity and substrate affinity. Substitution of Asn(171) and Asn(183) by aspartate individually caused no loss of BGT-1 activity, whereas the double mutant was inactive, suggesting that N-glycosylation of at least one of the sites is required for function. Substitution by alanine or valine at either site caused a dramatic loss in transport activity. Furthermore, in MDCK cells PM insertion of N183D was no longer regulated by osmotic stress, highlighting the impact of N-glycosylation in regulation of this SLC6 transporter.
MeSH term(s)	Amino Acid Sequence ; Animals ; Asparagine/metabolism ; Aspartic Acid/metabolism ; Betaine/metabolism ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Dogs ; Female ; Glycosylation ; HEK293 Cells ; Humans ; Kidney/metabolism ; Madin Darby Canine Kidney Cells ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oocytes/metabolism ; Osmotic Pressure ; Polysaccharides/metabolism ; Protein Transport ; Sequence Homology, Amino Acid ; Xenopus laevis ; gamma-Aminobutyric Acid/metabolism
Chemical Substances	Carrier Proteins ; Polysaccharides ; betaine plasma membrane transport proteins (146313-33-9) ; Aspartic Acid (30KYC7MIAI) ; Betaine (3SCV180C9W) ; gamma-Aminobutyric Acid (56-12-2) ; Asparagine (7006-34-0)
Language	English
Publishing date	2015-06-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2969-5
ISSN	1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
ISSN (online)	1470-8728
ISSN	0006-2936 ; 0306-3275 ; 0264-6021
DOI	10.1042/BJ20131031
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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Full text online

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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