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Rough Outline For Cotransporter Article[edit]

1. Introduction
2. Background
3. Structures & Composition
4. Mechanism
Antiporters vs Symporters
5 Examples of Cotransporters
Na+/glucose cotransporter (SGLT1) - is also known as sodium-glucose cotransporter 1 and are encoded by the SLC5A1 gene. SGLT1 is an electrogenic transporter as sodium electrochemical gradient drives glucose uphill into the cells. SGLT1 is a high affinity Na+ /glucose cotransporter that have an important role in transferring sugar across the epithelial cells of renal proximal tubule and of the intestine, in particular the small intestine.
Na+/phosphate cotransporter (NaPi) - Sodium-phosphate cotransporters are from SLC34 and SLC20 family. They are also found across the epithelial cells of renal proximal tubule and of the small intestine. It transfers inorganic phosphate into cells through active transport with the help of Na+ gradient. Simialar to SGTL1, they are classified as electrogenic transporters. NaPi couples by 3 Na+ ions and 1 divalent Pi, they classified as NaPi IIa and NaPi IIb. NaPi that couples with 2 Na+ and 1 divalent Pi are classified as NaPi IIc.
Na+/I- symporter (NIS) - Sodium-Iodide is a type of symporter that is responsible for transferring iodide in the thyroid gland. NIS is primarly found in cells of the thyroid gland and also in the mammary glands. They are located on the basolateral membrane of thryroid follicular cells where 2 Na+ ions and 1 I- ion is coupled to transfer the iodide. NIS activity helps in the diagnosis and treatment of thyroid disease, including the highly successful treatment of thyroid cancer with radioiodide after thyroidectomy.
Na+/K+/2Cl- cotransporter (NKCC) -
GABA transporter (GAT) - neurotransmitter γ-aminobutyric acid (GABA) transporter are members of the solute carrier family 6 (SLC6) of sodium- and chloride-dependent neurotransmitter receptor transporters that is located in the plasma membrane and regulate the concentration of GABA in the synaptic cleft. The SLC6A1 gene encodes for GABA transporters.
H+/oligopeptide transporter (PepT) -
Sodium-coupled bicarbonate cotransporters (NBC) -


6. Malfunction
Examples of conditions results from mutations
Transporter Symbols/Names Relevant Diseases
4F2HC, SLC3A2 Lysinuria
ABC-1, ABC1 Tangiers disease
ABC7, hABC7 X-linked sideroblastic anemia
ABCR Stargardt disease, Fundus flavimaculatus
AE1, SLC4A1 elliptocytosis, ovalocytosis, hemolytic anemia, spherocytosis, renal tubular acidosis
AE2, SLC4A2 congenital chloroidorrhea
AE3, SLC4A3 congenital chloroidorrhea
ALDR Adrenoleukodystrophy
ANK ankylosis (calcification); arthritis accompanied by mineral deposition, formation of bony outgrowths, and joint destruction
Aralar-like, SLC25A13 adult-onset type II citrullinemia
ATBo, SLC1A5, hATBo, ASCT2, AAAT Neurodegeneration
BCMP1, UCP4, SLC25A14 HHH
CFTR Cystic fibrosis
CTR-1, SLC31A1 Menkes/Wilsons disease
CTR-2, SLC31A2 Menkes/Wilsons disease, X-linked hypophosphatemia
DTD, SLC26A2 chondrodysplasias/ diadtrophic dysplasia
EAAT1, SLC1A3, GLAST1 Neurodegeneration, Amyotrophic lateral sclerosis
EAAT2, SLC1A2, GLT-1 Neurodegeneration, Dicarboxylic aminoaciduria
EAAT3, SLC1A1, EAAC1 Neurodegeneration
EAAT4, SLC1A6 Neurodegeneration
EAAT5, SLC1A7 Neurodegeneration
FIC1 Progressive familial intrahepatic cholestasis
FOLT, SLC19A1, RFC1 Folate malabsorption/megaloblastic anemia
GLUT1, SLC2A1 low CNS glucose causing seizures, Fanconi-Bickel syndrome, Glycogen storage disease type Id, Non-insulin-dependent diabetes mellitus, defect in glucose transport across the blood-brain barrier
GLUT2, SLC2A2 low CNS glucose causing seizures, Fanconi-Bickel syndrome, Glycogen storage disease type Id, Non-insulin-dependent diabetes mellitus (NIDDM)
GLUT3, SLC2A3 low CNS glucose causing seizures, Fanconi-Bickel syndrome, Glycogen storage disease type Id, Non-insulin-dependent diabetes mellitus (NIDDM)
GLUT4, SLC2A4 low CNS glucose causing seizures, Fanconi-Bickel syndrome, Glycogen storage disease type Id, Non-insulin-dependent diabetes mellitus (NIDDM)
GLUT5, SLC2A5 Isolated fructose malabsorption
HET anemia, genetic hemochromatosis
HTT, SLC6A4 anxiety-related traits
LAT-2, SLC7A6 Lysinuric protein intolerance
LAT-3, SLC7A7 lysinuric protein intolerance
MDR1 human cancers
MDR2, MDR3 Familia intrahepatic cholestasis
MRP1 human cancers
NBC Down’s syndrome
NBC1, SLC4A4 renal tubular acidosis
NBC3, SLC4A7 congenital hypothyroidism
NCCT, SLC12A3, TSC Gitelman syndrome
NHE2, SLC9A2 Microvillus inclusion disease
NHE3, SLC9A3/3P Microvillus inclusion disease
NIS, SLC5A5 congenital hypothyroidism
NKCC1, SLC12A2 gitelman’s syndrome
NKCC2, SLC12A1 Bartter’s syndrome
NORTR DiGeorge syndrome, velocardiofacial syndrome
NRAMP2, DCT1, SLC11A2, attention-deficit disorder
NTCP2, ISBT, SLC10A2 primary bile acid malabsorption (PBAM)
OCTN2, SLC22A5 systemic carnitine deficiency (progressive cardiomyopathy, skeletal myopathy, hypoglycaemia, hyperammonaemia, sudden infant death syndrome)
ORNT1, SLC25A15 HHH
PMP34, SLC25A17 Graves’ disease
rBAT, SLC3A1, D2 cystinuria
SATT, SLC1A4, ASCT1 Neurodegeneration
SBC2 hypocitraturia
SERT various mental disorders
SGLT1, SLC5A1 renal glucosuria / glucose-galactose malabsorption
SGLT2, SLC5A2 renal glucosuria
SMVT, SLC5A6 anxiety-related traits, depression
TAP1 juvenile onset psriasis
y+L Type I ystinuria


7. Summary Conclusions
8. Reference

Proposed References[edit]

By Sridenour

Hattori, T., Wang, P. (2006). Involvement of Na+-K+-2Cl- Cotransporters in Hypertonicity-Induced Rise in Intracellular Calcium Concentration. Intern. J. Neuroscience. 116: 1501-1507.

Discusses how activation of transport channels requires depolarization of the cell membrane. Obtained through JHU library so did not want to attach the PDF since access is limited to students and employees.

Lionetta, M.G., Chettino, T. (2006). The Na+-K-2Cl- cotransporter and the osmotic stress response in a model salt transport epithelium. Acta Physiol. 187: 115-124.

Talks about this specific contransport channel and its role in maintaining the water and electrolyte content of the cell. Obtained through JHU library so did not want to attach the PDF since access is limited to students and employees.

Werner, A., Dehmelt, L., Nalbant, P. (1998). Na+-Dependent Phosphate Cotransporters: The NaPi Protein Families. The Journal of Experimental Biology. 201: 3135-3142. [1]

Talks about the specific families of Na+/Pi contransporters.

Hubner, C.A., Jentsch, T.J. (2002). Ion Channel Diseases. Human Molecular Genetics. 11(20): 2435-2445 [2]

Has a good list of diseases caused by defects within various channels.

Berridge, M.J. (2012). Cell Signalling Biology; doi:10.1042/csb0001003 [3]

Great website discussing in depth all various types of ion channels. Has various sections devoted to specific cotransporters. May also be able to take some pictures from this page but I need to review the copyright availability first before posting them.

Proposed References[edit]

By Lutyeus

Lodish, H., Berk, A., Amon, A., Bretscher, A., Kaiser, C., Kriefer, M., et al. (2013). Molecular Cell Biology (7th ed.). New York: W.H. Freeman and Co..

  • Page 476 has a simple definition
  • Page 502 compares cotransporters with uniporters
  • many, many good visualizations, just will need to site correctly

Gao, X., Zhou, L., Jiao, X., Lu, F., Yan, C., Zeng, X., et al. (2010). Mechanism Of Substrate Recognition And Transport By An Amino Acid Antiporter. Nature, 463(7282), 828-832. here

  • Describes how substrate recognition occurs before any conformational changes are possible allowing for cotransport

Gao, X., Lu, F., Zhou, L., Dang, S., Sun, L., Li, X., et al. (2009). Structure And Mechanism Of An Amino Acid Antiporter. Science, 324(5934), 1565-1568. here

  • Describes the mechanism of action and general structure of antiporters which are a type of cotransporter

Wright, E. (2001). Renal Na+ -glucose cotransporters. American Journal of Physiology - Renal Physiology, 280(F) 10-18.here

  • talks about sodium/glucose cotransporters in renal cells
  • covers protein structure
  • gene information
  • transport mechanisms
  • good visuals

Haas, M. (1994). The Na-K-Cl cotransporters. American Journal of Physiology - Cell Physiology, 267(C) 869-885. here

  • very important mechanism many cells, particularly muscle cells
  • covers mechanism
  • general structure of Na-K-Cl cotransporters, not just a specific one, this is very useful for us
  • methods of regulation, which include protein kinases and phosphatates
  • primary and secondary cotransport activation
  • signalling

Possible Images[edit]

By Lutyeus

this is a nice image but I have seen it all over the place and can't find any information on if it is copyrighted...
not the best image but already available in wikimedia commons
excellent .gif demonstrating a sympoter
already on wikimedia commons
only problem is the very beginning is in another language


By Harshil

Has pictures and videos of cell membrane
Picture of the gene SLC4A7 solute carrier family 4, sodium bicarbonate cotransporter, member 7, Homo sapiens


By Sonya

Has a great picture of the six secondary active cotransporters

I also found this one already uploaded in wikimedia commons and thought it is a pretty basic picture of the three types of transporters.

caption transporters






Proposed References[edit]

By Harshil


1) http://www.infosources.org/what_is/Robert_K._Crane.html

- About Robert K Crane - who discovered the cotransport system, can go under Background section of the topic.

2) Édith Gagnon, Biff Forbush, Luc Caron, & Paul Isenring, 2003, Functional comparison of renal Na-K-Cl cotransporters between distant species, Vol. 284, American Journal of Physiology, Cell Physiology Published, pp. 365-370.

- Article on comparing the cotransporters among different species.

3) http://omim.org/entry/603353

- Information on Sodium bicarbonate cotransporter

4) Maa-Ohui Quarmyne, Mary Risinger, Andrew Linkugel, Anna Frazier, & Clinton Joiner, 2011, Defining A Phenotype for Red Cel Volume Regualtion and Potassium Chloride Cotransport, Vol 47, No. 2, Blood Cells Mol Dis, pp 95-99.

- Information on Potassium Chloride cotranspoter

5) Naomi Mizuno, Takuro Niwa, Yoshihisa Yotsumoto, & Yuichi Sugiyama, 2003, Impact of Drug Transporter Studies on Drug Discovery and Development, Vol. 55, No. 3, Pharmacological reviews, The American Society for Pharmacology and Experimental Therapeutics, pp.425-461.

- Application of cotransporter, this article has information on durg delivery through cotransporter.

6) Blaustein, Mordecai, 1984, Sodium transport and hypertension. Where we going?, Vol. 6 No. 4, Hypertension, American Heart Association, pp.445-453.

- Topic on the sodium cotransporter assocaited with hypertension.

7) Ellory, J.C. and Stweart, G.W.,1982, The Human Erythrocyte C1-Dependent Na-K Cotransport System As A Possible Model Foe Studying The Action Of Loop Diuretics,Vol.75, British Journal of Pharmacology, pp. 183–188.

- Supporting article to hypertension and cotranporter.

8) Kirk L. Hamilton, 2013, RobertK.Crane—Na+-glucosecotransportertocure?, March, Vol. 4, Article 53, Frontiers in Physiology, pp.1-5.

- Has information on Robert K Crane - discovery of cotransport.
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