Symporters

Publication Title: 
The Biochemical Journal

NaCT (sodium-coupled citrate transporter) is an Na(+)-coupled citrate transporter identified recently in mammals that mediates the cellular uptake of citrate. It is expressed predominantly in the liver. NaCT is structurally and functionally related to the product of the Indy (I'm not dead yet) gene in Drosophila, the dysfunction of which leads to lifespan extension. Here, we show that NaCT mediates the utilization of extracellular citrate for fat synthesis in human liver cells, and that the process is stimulated by lithium.

Author(s): 
Inoue, Katsuhisa
Zhuang, Lina
Maddox, Dennis M.
Smith, Sylvia B.
Ganapathy, Vadivel
Publication Title: 
Molecular Aspects of Medicine

The SLC16 gene family has fourteen members. Four (SLC16A1, SLC16A3, SLC16A7, and SLC16A8) encode monocarboxylate transporters (MCT1, MCT4, MCT2, and MCT3, respectively) catalysing the proton-linked transport of monocarboxylates such as l-lactate, pyruvate and ketone bodies across the plasma membrane. SLC16A2 encodes a high affinity thyroid hormone transporter (MCT8) and SLC16A10 an aromatic amino acid transporter (TAT1). The substrates and roles of the remaining eight members are unknown.

Author(s): 
Halestrap, Andrew P.
Publication Title: 
Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology

The human potassium-chloride co-transporter 3 (KCC3, SLC12A6) is involved in cell proliferation and in electro-neutral movement of ions across the cell membrane. The gene (SLC12A6) is located on chromosome 15q14, a region that has previously shown linkage with bipolar disorder, schizophrenia, rolandic epilepsy, idiopathic generalized epilepsy, autism and attention deficit/hyperactivity disorder. Furthermore, recessively inherited mutations of SLC12A6 cause Andermann syndrome, characterized by agenesis of the corpus callosum, which is associated with peripheral neuropathy and psychoses.

Author(s): 
Moser, Dirk
Ekawardhani, Savira
Kumsta, Robert
Palmason, Haukur
Bock, Christoph
Athanassiadou, Zoi
Lesch, Klaus-Peter
Meyer, Jobst
Publication Title: 
Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology

GABA(A) receptors mediate both fast phasic inhibitory postsynaptic potentials and slower tonic extrasynaptic inhibition. Hyperpolarizing phasic GABAergic inhibition requires the activity of neuron-specific chloride-extruding potassium-chloride cotransporter KCC2 in adult CNS. However, the possible role of KCC2 in tonic GABAergic inhibition and the associated behaviors is unknown.

Author(s): 
Tornberg, Janne
Segerstråle, Mikael
Kulesskaya, Natalia
Voikar, Vootele
Taira, Tomi
Airaksinen, Matti S.
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

Amoxicillin and cefaclor are two of the widely used beta-lactam antibiotics in the treatment of urinary tract infections. Both drugs are eliminated mainly by the kidney and rely on renal excretion to exert their antibacterial activities in the urinary tract. Previous studies have suggested the involvement of organic anion and oligopeptide transporters in membrane transport of beta-lactams.

Author(s): 
Li, Meng
Anderson, Gail D.
Phillips, Brian R.
Kong, Wei
Shen, Danny D.
Wang, Joanne
Publication Title: 
American Journal of Physiology. Cell Physiology

Transport and distribution of vitamin C is primarily regulated by the function of sodium-dependent vitamin C transporters (SVCTs). SVCT1 is expressed in the small intestine, liver, and kidney, organs that play a vital role in whole body vitamin C homeostasis. Despite the importance of this protein, little is known about regulation of the gene encoding SVCT1, Slc23a1. In this study, we present the first investigation of the transcriptional regulation of human Slc23a1, identifying transcription factors that may influence its expression.

Author(s): 
Michels, Alexander J.
Hagen, Tory M.
Publication Title: 
Science (New York, N.Y.)

Aging is genetically determined and environmentally modulated. In a study of longevity in the adult fruit fly, Drosophila melanogaster, we found that five independent P-element insertional mutations in a single gene resulted in a near doubling of the average adult life-span without a decline in fertility or physical activity. Sequence analysis revealed that the product of this gene, named Indy (for I'm not dead yet), is most closely related to a mammalian sodium dicarboxylate cotransporter-a membrane protein that transports Krebs cycle intermediates.

Author(s): 
Rogina, B.
Reenan, R. A.
Nilsen, S. P.
Helfand, S. L.
Publication Title: 
The Biochemical Journal

Indy is a gene in Drosophila melanogaster which, when made dysfunctional, leads to an extension of the average adult life span of the organism. The present study was undertaken to clone the Indy gene-product and to establish its functional identity. We isolated a full-length Indy cDNA from a D. melanogaster cDNA library. The cDNA codes for a protein of 572 amino acids [( Drosophila Indy (drIndy)]. In its amino acid sequence, drIndy exhibits comparable similarity to the two known Na(+)-coupled dicarboxylate transporters in mammals; namely, NaDC1 (35% identity) and NaDC3 (34% identity).

Author(s): 
Inoue, Katsuhisa
Fei, You-Jun
Huang, Wei
Zhuang, Lina
Chen, Zhong
Ganapathy, Vadivel
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Caloric restriction extends life span in a variety of species, highlighting the importance of energy balance in aging. A new longevity gene, Indy (for I'm not dead yet), which doubles the average life span of flies without a loss of fertility or physical activity, was postulated to extend life by affecting intermediary metabolism.

Author(s): 
Knauf, Felix
Rogina, Blanka
Jiang, Zhirong
Aronson, Peter S.
Helfand, Stephen L.
Publication Title: 
The Journal of Biological Chemistry

We have cloned and functionally characterized two Na(+)-coupled dicarboxylate transporters, namely ceNaDC1 and ceNaDC2, from Caenorhabditis elegans. These two transporters show significant sequence homology with the product of the Indy gene identified in Drosophila melanogaster and with the Na(+)-coupled dicarboxylate transporters NaDC1 and NaDC3 identified in mammals. In a mammalian cell heterologous expression system, the cloned ceNaDC1 and ceNaDC2 mediate Na(+)-coupled transport of various dicarboxylates.

Author(s): 
Fei, You-Jun
Inoue, Katsuhisa
Ganapathy, Vadivel

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