Choline is an essential nutrient for all cells because it plays a role in the synthesis of the membrane phospholipid components of the cell membranes, as a methyl-group donor in methionine metabolism as well as in the synthesis of the neurotransmitter acetylcholine. Choline deficiency affects the expression of genes involved in cell proliferation, differentiation, and apoptosis, and it has been associated with liver dysfunction and cancer. Abnormal choline transport and metabolism have been implicated in a number of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Therefore, the study of choline transport and the characteristics of choline transporters are of central importance to understanding the mechanisms that underlie membrane integrity and cell signaling in such disorders. Kinetic studies with radiolabeled choline and inhibitors distinguish three systems for choline transport: (i) low-affinity facilitated diffusion, (ii) high-affinity, Na+-dependent transport, and (iii) intermediate-affinity, Na+-independent transport. It is only recently, however, that the proteins having transport characteristics of at least one of these systems have been identified. They include (i) polyspecific organic cation transporters (OCTs) with low affinity for choline, (ii) high-affinity choline transporters (CHT1s), and (iii) intermediate-affinity choline transporter-like (CTL1) proteins. CHT1 and CTL1 but not OCT transporters are selectively inhibited with hemicholinium-3 and essentially display characteristics of specialized transporters for targeted choline metabolism. CHT1 is abundant in neurons and almost exclusively supplies choline for acetylcholine synthesis. The focus here is more on newly-discovered CTL1 choline transporters. They are expressed in different organisms and cell types, apparently not for the biosynthesis of acetylcholine but for the production of the most abundant metabolite of choline, the membrane lipid phosphatidylcholine.
SheardNF, ZeiselSH. Choline: an essential dietary nutrient?Nutrition5: 1–5, 1989.
3.
SweetDH, MillerDS, PritchardJB. Ventricular choline transport—a role for organic cation transporter 2 expressed in choroids plexus. J Biol Chem276: 41611–416119, 2001.
4.
ZeiselSH, da CostaKA, FranklinPD, AlexanderEA, LamontJT, SheardNF, BeiserA. Choline: an essential nutrient for humans. FASEB J5: 2093–2098, 1991.
5.
ZeiselSH. Choline: essential for brain development and function. Adv Pediatr44: 263–295, 1997.
6.
ZeiselSH, BlusztajnJK. Choline and human nutrition. Annu Rev Nutr14: 269–296, 1994.
7.
FisherMC, ZeiselSH, MarMH, SadlerTW. Inhibitors of choline uptake and metabolism cause developmental abnormalities in neurulating mouse embryos. Teratology64: 114–122, 2001.
8.
BlusztajnJK, WurtmanRJ. Choline and cholinergic neurons. Science221: 614–620, 1983.
9.
WesslerI, KilbingerH, BittengerF, KirkpatrickCJ. The biological role of non-neuronal acetylcholine in plants and humans. J Pharmacol85: 2–10, 2001.
10.
WesslerI, KirkpatrickCJ, RackéK. Non-neuronal acetylcholine, a locally acting molecule, widely distributed in biological systems: expression and function in humans. Pharmacol Ther77: 59–79, 1998.
11.
Institute of Medicine, and National Academy of Sciences of the USA. Dietary Reference Intakes for Folate, Thiamin, Riboflavin, Niacin, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academic Press, Vol. 1: 390–422, 1998.
12.
ZeiselSH, MarMH, HoweJC, HoldenJM. Concentrations of choline-containing compounds and betaine in common foods. J Nutr133: 1302–1307, 2003.
GarnerSC, MarMH, ZeiselSH. Choline distribution and metabolism in pregnant rats and fetuses are influenced by the choline content of the maternal diet. J Nutr125: 2851–2858, 1995.
15.
CermakJM, BlusztajnJK, MeckWH, WilliamsCL, FitzgeraldCM, RoseneDL, LoyR. Prenatal availability of choline alters the development of acetylcholinesterase in the rat hippocampus. Dev Neurosci21: 94–104, 1999.
16.
FischerLM, ScearceJA, MarMH, PatelJR, BlanchardRT, MacintoshBA, BusbyMG, ZeiselSH. Ad libitum choline intake in healthy individuals meets or exceeds the proposed adequate intake level. J Nutr135: 826–829, 2005.
17.
ZeiselSH. Choline, homocysteine and pregnancy. Am J Clin Nutr82: 719–720, 2005.
18.
ZeiselSH. Choline: an essential nutrient for humans. Nutrition16: 669–671, 2000.
19.
ZeiselSH. Choline: a nutrient that is involved in the regulation of cell proliferation, cell death, and cell transformation. In: HeberD, KritchevskyD, Eds. Dietary Fats, Lipids, Hormones and Tumorigenesis. New York: Plenum Press, pp 131–141, 1996.
20.
AlbrightCD, LiuR, BetheaTC, Da CostaKA, SalganikRI, ZeiselSH. Choline deficiency induces apoptosis in SV-40 immortalized CWSV-1 rat hepatocytes in culture. FASEB J10: 510–516, 1996.
21.
ZeiselSH, AlbrightCD, ShinOH, MarMH, SalganikRI, da CostaKA. Choline deficiency selects for resistance to p53-independent apoptosis and causes tumorigenic transformation of rat hepatocytes. Carcinogenesis18: 731–738, 1997.
22.
GuoWX, PyeQN, WilliamsonKS, StewartCA, HensleyKL, KotakeY, FloydRA, BroylesRH. Mitochondrial dysfunction in choline deficiency-induced apoptosis in cultured rat hepatocytes. Free Radic Biol Med39: 641–650, 2005.
23.
Holmes-McNaryMQ, BaldwinASJr., ZeiselSH. Opposing regulation of choline deficiency-induced apoptosis by p53 and nuclear factor κB. J Biol Chem276: 41197–41204, 2001
24.
NiculescuMD, CraciunescuCN, ZeiselSH. Gene expression profiling of choline-deprived neural precursor cells isolated from mouse brain. Brain Res Mol Brain Res134: 309–322, 2005.
25.
KashireddyPR, RaoMS. Sex differences in choline-deficient diet-induced steatohepatitis in mice. Exp Biol Med (Maywood)229: 158–162, 2004.
26.
Da CostaKA, GaffneyCE, FischerLM, ZeiselSH. Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load. Am J Clin Nutr81: 440–444, 2005.
27.
KohlmeierM, da CostaKA, FischerLM, ZeiselSH. Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans. Proc Natl Acad Sci U S A102: 16025–16030, 2005.
28.
HoffmannK, GrafeF, WohlrabW, NeubertRH, BrandschM. Functional characterization of a high-affinity choline transport system in human keratinocytes. J Invest Dermatol119: 118–121, 2002.
29.
ZeiselSH. Choline: an important nutrient in brain development, liver function and carcinogenesis. J Am Coll Nutr11: 473–481, 1992.
30.
JacobsRL, DevlinC, TabasI, VanceDE. Targeted deletion of hepatic CTP:phosphocholine cytidylyltransferase alpha in mice decreases plasma high density and very low density lipoproteins. J Biol Chem279: 47402–47410, 2004.
31.
DavisCD, UthusEO. DNA methylation, cancer susceptibility, and nutrient interactions. Exp Biol Med (Maywood)229: 988–995, 2004.
32.
RayJG, LaskinCA. Folic acid and homocystine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: a systematic review. Placenta20: 519–529, 1999.
33.
Velzing-AartsFV, HolmPI, FokkemaMR, van der DijsFP, UelandPM, MuskietFA. Plasma choline and betaine and their relation to plasma homocysteine in normal pregnancy. Am J Clin Nutr81: 1383–1389, 2005.
34.
MolloyAM, MillsJL, CoxC, DalySF, ConleyM, BrodyLC, KirkePN, ScottJM, UelandPM. Choline and homocysteine interrelations in umbilical cord and maternal plasma at delivery. Am J Clin Nutr82: 836–842, 2005.
35.
MeckWH, WilliamsCL. Simultaneous temporal processing is sensitive to prenatal choline availability in mature and aged rats. Neuroreport8: 3045–3051, 1997.
36.
MeckWH, WilliamsCL. Characterization of the facilitative effects of perinatal choline supplementation on timing and temporal memory. Neuroreport8: 2831–2835, 1997.
37.
MeckWH, SmithRA, WilliamsCL. Organizational changes in cholinergic activity and enhanced visuospatial memory as a function of choline administered prenatally or postnatally or both. Behav Neurosci103: 1234–1241, 1989.
38.
ShawGM, CarmichaelSL, YangW, SelvinS, SchafferDM. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am J Epidemiol160: 102–109, 2004.
39.
KentC. Regulatory enzymes of phosphatidylcholine biosynthesis: a personal perspective. Biochim Biophys Acta1733: 53–66, 2005.
40.
AoyamaC, LiaoH, IshidateKStructure and function of choline kinase isoforms in mammalian cells. Prog Lipid Res43: 266–281, 2004.
VanceJE, VanceDE. Metabolic insights into phospholipids function using gene-targeted mice. J Biol Chem280: 10877–10880, 2005.
43.
JackowskiS, FagoneP. CTP:phosphocholine cytidylyltransferase: paving the way from gene to membrane. J Biol Chem280: 853–856, 2005.
44.
BakovicM, WaiteK, TangW, TabasI, VanceDE. Transcriptional activation of the murine CTP:phosphocholine cytidylyltransferase gene (Ctpct): combined action of upstream stimulatory and inhibitory cis-acting elements. Biochim Biophys Acta1438: 147–165, 1999.
45.
GolfmanLS, BakovicM, VanceDE. Transcription of the CTP: phosphocholine cytidylyltransferase alpha gene is enhanced during the S phase of the cell cycle. J Biol Chem276: 43688–43692, 2001.
46.
BakovicM, WaiteK, VanceDE. Oncogenic Ha-Ras transformation modulates the transcription of the CTP:phosphocholine cytidylyltransferase alpha gene via p42/44MAPK and transcription factor Sp3. J Biol Chem278: 14753–14761, 2003.
47.
VanceDE. Phosphatidylethanolamine N-methyltransferase: unexpected findings from curiosity-driven research. Eur J Med Res1: 182–188, 1996.
NogaAA, SteadLM, ZhaoY, BrosnanME, BrosnanJT, VanceDE. Plasma homocysteine is regulated by phospholipid methylation. J Biol Chem278, 5952–5955, 2003.
51.
NogaAA, VanceDE. A gender-specific role for phosphatidylethanolamine N-methyltransferase-derived phosphatidylcholine in the regulation of plasma high density and very low density lipoproteins in mice. J Biol Chem278: 21851–21859, 2003.
RileySP, TalbotNJ, AhmedMJ, JouhalK, HendryBM. Characterization of human erythrocyte choline transport in chronic renal failure. Nephrol Dial Transplant12: 1921–1927, 1997.
54.
HendryBM. Membrane transport in uraemia. In: RaineAEG, Ed. Advanced Renal Medicine. New York: Oxford University Press, pp 16–24, 1992.
55.
IorioE, MezzanzanicaD, AlbertiP, SpadaroF, RamoniC, D'ascenzoS, MillimaggiD, PavanA, DoloV, CanevariS, PodoF. Alterations of choline phospholipid metabolism in ovarian tumor progression. Cancer Res65: 9369–9376, 2005.
WeckerL. Dietary choline. A limiting factor for the synthesis of acetylcholine by the brain. Adv Neurol51: 139–145, 1990.
58.
SlotkinTA, NemeroffCB, BissetteG, SeidlerFJ. Overexpression of the high affinity choline transporter in cortical regions affected by Alzheimer's disease. Evidence from rapid autopsy studies. J Clin Invest94: 696–702, 1994.
59.
MillerBL, JendenDJ, CummingsJL, ReadS, RiceK, BensonDF. Abnormal erythrocyte choline and influx in Alzheimer's diseaseLife Sci10: 485–490. 1986.
60.
ManyamBV, GiacobiniE, ColliverJA. Cerebrospinal fluid choline levels are decreased in Parkinson's disease. Ann Neurol27: 683–685, 1993.
61.
ManyamBV, GiacobiniE, ColliverJA. Cerebrospinal fluid acetylcholine-esterase and choline measurements in Huntington's disease. J Neurol237: 281–284, 1990.
62.
BarbeauA. Friedreich's ataxia 1979: an overview. Can J Neurol Sci6: 311–319, 1979.
63.
FisherAB, DodiaC, ChanderA, KleinzellerA. Transport of choline by plasma membrane vesicles from lung-derived epithelial cells. Am J Physiol263: C1250–C1257, 1992.
64.
DevesR, KrupkerRM. The binding and translocation steps in transport as related to substrate structure. A study of choline carrier of erythrocytes. Biochim Biophys Acta557: 468–485, 1979.
65.
SimonJR, AtwehS, KuharMJ. Sodium-dependent, high affinity choline uptake: a regulatory step in the synthesis of acetylcholine. J Neurochem26: 909–922, 1976.
66.
GrasslSM. Choline transport in human placental brush-border membrane vesicles. Biochim Biophys Acta1194: 203–213, 1994.
67.
PorterRK, ScottJM, BrandMD. Choline transport into rat liver mitochondria. Characterization and kinetics of a specific transporter. J Biol Chem267: 14637–14646, 1992.
68.
Van RossumGDV, BoydCAR. Sodium-dependent and -independent choline uptake by type II epithelial cells from rat lung. J Membr Biol162: 147–156, 1998.
69.
Van GoldeLMG. Metabolism of phospholipids in the lung. Am Rev Respir Dis114: 977–1000, 1976.
70.
JohnsonRG, LuggMA, NicholasTE. Uptake of [14C]-choline and incorporation into lung phospholipids by the isolated rat lung. Lipids14: 555–558, 1978.
71.
YostRW, ChanderA, DodiaC, FisherAB. Synthesis of phosphatidylcholine by rat lung during choline deficiency. J Appl Physiol61: 2040–2044, 1986.
72.
KleinJ, KoppenA, LoffelholzK, SchmitthennerJ. Uptake and metabolism of choline by rat brain after acute choline administration. J Neurochem58: 870–876, 1992.
73.
WurtmanRJ. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons. Trends Neurosci15: 117–122, 1992.
74.
ZeiselSH, MarMH, ZhouZ, da CostaKA. Pregnancy and lactation are associated with diminished concentrations of choline and its metabolites in rat liver. J Nutr125: 3049–3054, 1995.
75.
WelschF. Choline metabolism in human term placenta. Biochem Pharmacol27: 1251–1257, 1978.
76.
MüllerJ, BornI, NeubertRH, BrandschM. Apical uptake of choline and cationic drugs in epithelial cell lines derived from human placenta. Placenta26: 183–189, 2005.
77.
KwonY, LeeRD, MorrisME. Hepatic uptake of choline in rat liver basolateral and canalicular membrane vesicle preparations. J Pharmacol Exp Ther279: 774–778, 1996.
78.
SinclairCJ, ChiKD, SubramanianV, WardKL, GreenRM. Functional expression of a high affinity mammalian hepatic choline/organic cation transporterJ Lipid Res41: 1841–1848, 2000.
79.
DantzlerWH, EvansKK, WrightSH. Basolateral choline transport in isolated rabbit renal proximal tubules. Pflugers Arch436: 899–905, 1998.
80.
AcaraM. The kidney in the regulation of plasma choline in the chicken. Am J Physiol228: 645–649, 1975.
81.
NagelG, VolkC, FriedrichT, UlzheimerJC, BambergE, KoepsellH. A reevaluation of substrate specificity of the rat cation ransporter rOCT1. J Biol Chem272: 31953–31956, 1997.
82.
WrightSH, DantzlerWH. Molecular and cellular physiology of renal organic cation and anion transport. Physiol Rev84: 987–1049, 2004.
83.
FergusonSM, BlakelyRD. The choline transporter resurfaces: new roles for synaptic vesicles?Mol Interv4: 22–37, 2004.
WarburtonEC, KoderT, ChoK, MasseyPV, DuguidG, BarkerGRI, AggletonJP, BashirZI, BrownMW. Cholinergic neurontransmission is essential for perirhinal cortical plasticity and recognition memory. Neuron38: 987–996, 2003.
88.
XieJ, GuoQ. Par-4 inhibits choline uptake by interacting with CHT1 and reducing its incorporation to the plasma membrane. J Biol Chem279: 28266–28275, 2004.
89.
OkudaT, HagaT, KanaiY, EndouH, IshiharaT, KatsuraI. Identification and characterization of the high affinity choline transporter. Nat Neurosci3: 120–125, 2000.
90.
ApparsundaramS, FergusonSM, GeorgeALJr., BlakelyRD. Molecular cloning of a human, hemicholinium-3-sensitive choline transporter. Biochem Biophys Res Commun276: 862–867, 2000.
91.
OkudaT, HagaT. Functional characterization of the human high-affinity choline tranporter. FEBS Lett484: 92–97, 2000.
92.
WangY, CaoZ, NewkirkRF, IvyMT, TownselJG. Molecular cloning of a cDNA for a putative choline co-tansporter from Limulus CNS. Gene268: 123–131, 2001.
93.
ApparsundaramS, FergusonSM, BlakelyRD. Molecular cloning and characterization of a murine hemicholinium-3-sensitive choline transporter. Biochem Soc Trans29: 711–716, 2001.
PfeilU, HaberbergerRV, LipsKS, EberlingL, GrauV, KummerW. Expression of the high-affinity choline transporter CHT1 in epithelia. Life Sci72: 2087–2090, 2003.
96.
PfeilU, LipsKS, EberlingL, GrauV, HaberbergerRV, KummerW. Expression of the high-affinity choline transporter, CHT1, in the rat trachea. Am J Respir Cell Mol Biol28: 473–477, 2003.
97.
HaberbergerRV, PfeilU, LipsKS, KummerW. Expression of the high-affinity choline transporter, CHT1, in the neuronal and non-neuronal cholinergic system of human and rat skin. J Invest Dermatol119: 943–948, 2002.
98.
BarkerLA. Modulation of synaptosomal high affinity choline transport. Life Sci18: 725–731, 1976.
99.
MurrinLC, KuharMJ. Activation of high-affinity choline uptake in vitro by depolarizing agents. Mol Pharmacol12: 1082–1090, 1976.
100.
RoskoskiRJr.. Acceleration of choline uptake after depolarization-induced acetylcholine release in rat cortical synaptosomes. J Neurochem30: 1357–1361, 1978.
101.
ShermanKA, ZigmondMJ, HaninI. High affinity choline uptake in striatum and hippocampus: differential affects of treatments which release acetylcholine. Life Sci23: 1863–1870, 1978.
102.
O'reganS, CollierB. Factors affecting choline transport by the cat superior cervical ganglion during and following stimulation, and the relationship between choline uptake and acetylcholine synthesis. Neuroscience6: 511–520, 1981.
103.
CancelaJM, BertrandN, BeleyA. Involvement of cAMP in the regulation of high affinity choline uptake by rat brain synaptosomes. Biochem Biophys Res Commun213: 944–949, 1995.
104.
VolgelsbergV, NeffNH, HadjiconstantinovM. Cyclic AMP-mediated enhancement of high-affinity choline transport and acetylcholine synthesis in brain. J Neurochem68: 1062–1070, 1997.
105.
FordBD, IvyMT, MtshaliCP, TownselJG. The involvement of protein kinase C in the regulation of choline cotransport in Limulus. Comp Biochem Physiol A Mol Integr Physiol123: 255–261, 1999.
106.
GuyenetP, LefresneP, RossierJ, BeaujouanJC, GlowinskiJ. Inhibition by hemicholinium-3 of (14C)acetylcholine synthesis and (3H)choline high-affinity uptake in rat striatal synaptosomes. Mol Pharmacol9: 630–639, 1973.
107.
LowensteinPR, CoyleJT. Rapid regulation of [3H] hemicholinium-3 binding sites in the rat brain. Brain Res381: 191–194, 1986.
108.
CookeLJ, RylettRJ. Inhibitiors of serine/threonine phosphatases increase membrane bound choline acetyltransferase activity and enhance acetylcholine synthesis. Brain Res751: 232–238, 1997.
Diaz-MecoMT, MunicioMM, FrutosS, SanchezP, LozanoJ, SanzL, MoscatJ. The product of par-4, a gene induced during apoptosis, interacts selectively with the atypical isoforms of protein kinase C. Cell86: 777–786, 1996.
111.
SellsSF, HanSS, MuthukkumarS, MaddiwarN, JohnstoneR, BoghaertE, GillsD, LiuG, NairP, MonnigS, ColliniP, MattsonMP, SukhatmeVP, ZimmerSG, WoodDVJr., McRobertsJW, ShiY, RangnekarVM. Expression and function of the leucine zipper protein par-4 in apoptosis. Mol Cell Biol17: 3823–3832, 1997.
112.
GuoQ, FuW, XieJ, LuoH, SellsSF, GeddesJW, BondadaV, RangnekarVM, MattsonMP. Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease. Nat Med4: 957–962, 1994.
113.
ChanSL, TammarielloSP, EstusS, MattsonMP. Prostate apoptosis response-4 mediates trophic factor withdrawal-induced apoptosis of hippocampal neurons: actions prior to mitochondrial dysfunction and caspase activation. J Neurochem73: 502–512, 1999.
114.
MattsonMP, DuanW, ChanSL, CamandolaS. Par-4: an emerging pivotal player in neuronal apoptosis and neurodegenerative disorders. J Mol Neurosci13: 17–30, 1999.
115.
GuoQ, SebastianL, SopherBL, MillerMW, GlaznerGW, WareCB, MartinGM, MattsonMP. Neurotrophic factors [activity-dependent neurotrophic factor (ADNF) and basic fibroblast growth factor (bFGF)] interrupt excitotoxic neurodegenerative cascades promoted by a PS1 mutation. Proc Natl Acad Sci U S A96: 4125–4130, 1999.
116.
GuoQ, XieJ, ChangX, DuH. Prostate apoptosis response-4 enhances secretion of amyloid β peptide 1–42 in human neuroblastomas IMR-32 cells by a caspase-dependent pathway. J Biol Chem276: 16040–16044, 2001.
117.
FergusonSM, BazalakovaM, SavchenkoV, TapiaJC, WrightJ, BlakelyRD. Lethal impairment of cholinergic neurotransmission in hemicholinium-3-sensitive choline transporter knockout mice. Proc Natl Acad Sci U S A101: 8762–8767, 2004.
118.
JonkerJW, WagenaarE, MolCAAM, BuitelaarM, KoepsellH, SmitJW, SchinkelAH. Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of organic cation transporter 1 (Oct1[Slc 22a1]) gene. Mol Cell Biol21: 5471–5477, 2001.
119.
GrundemannD, GorboulevV, GambaryanS, VehylM, KoepsellH. Drug excretion mediated by a new prototype of polyspecific transporter. Nature372: 549–552, 1994.
120.
GorboulevV, UlzheimerJC, AkhoundovaA, Ulzheimer-TeuberI, KarbachU, QuesterS, BaumannC, LangF, BuschAE, KoepsellH. Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol16: 871–881, 1997.
121.
SchweifeN, BarlowDP. The Lx1 gene maps to mouse chromosome 17 and codes for a protein that is homologous to glucose and polyspecific transmembrane transporters. Mamm Genome7: 735–740, 1996.
122.
OkudaM, SaitoH, UrakamiY, TakanoM, InuiK. cDNA doing and functional expression of a novel rat kidney organic cation transporter, OCT2. Biochem Biophys Res Commun224: 500–507, 1996.
123.
WuX, KekudaR, HuangW, FeiYJ, LeibachFH, ChenJ, ConwaySJ, GanapathyV. Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem273: 32776–32786, 1998.
124.
KakehiM, KoyabuN, NakamuraT, UchiumiT, KuwanoM, OhtaniH, SawadaY. Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. Biochem Biophys Res Commun296: 644–650, 2002.
125.
GrundemannD, Babin-EbellJ, MartelF, ÖrdingN, SchmidtA, SchömigE. Primary structure and functional expression of the apical organic cation transporter from kidney epithelial LLC-PK1 Cells. J Biol Chem272: 10408–10413, 1997.
126.
TerashitaS, DresserMJ, ZhangL, GrayAT, YostSC, GiacominiKM. Molecular cloning and functional expression of a rabbit renal organic cation transporter. Biochim Biophys Acta1369: 1–6, 1998.
127.
TamaiI, YabuuchaiH, NezuJ, SaiY, OkuA, ShimaneM, TsujiA. Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1. FEBS Lett419: 107–111, 1997.
128.
WuX, PrasadPD, LeibachFH, GanapathyV. cDNA sequence, transport function, and genomic organizztion of human OCTn2, a new member of the organic cation transporter family. Biochem Biophys Res Commun246: 589–595, 1998.
129.
Meyer-WentrupF, KarbachU, GorboulevV, AmdtP, KoepsellH. Membrane localization of the electrogenic cation transporter rOCT1 in rat liver. Biochem Biophys Res Commun248: 673–678, 1998.
130.
KarbachU, KrickeJ, Meyer-WentrupF, GorboulevV, VolkC, Loffing-CueniD, KaisslingB, BachmannS, KoepsellH. Localization of organic cation transporters OCT1 and OCT2 in rat kidney. Am J Physiol Renal Physiol279: F679–F687, 2000.
131.
GrundemannD, KosterS, KieferN, BreidertT, EngelhardtM, SpitzenbergerF, ObermullerN, SchomigE. Transport of monoamine transmitters by the organic cation transporter type 2, OCT2. J Biol Chem273: 30915–30920, 1998.
132.
KekudaR, PrasadPD, WuX, WangH, FeiY, LeibachFH, GanapathyV. Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J Biol Chem273: 15971–15979, 1998.
133.
KoepsellH, GorboulevV, AmdtP. Molecular pharmacology of organic cation transporters in kidney. J Membr Biol167: 103–117, 1999.
SweetDH, MillerDS, PritchardJB. Ventricular choline transport, a role for organic cation transporter 2 expressed in choroids plexus. J Biol Chem276: 41611–41619, 2001.
136.
ZhangL, SchanerME, GiacominiKM. Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther286: 354–361, 1998.
137.
MartelF, VetterT, RussH, GrundemannD, AzevedoI, KoepsellH, SchomigE. Transport of small organic cations in the rat liver. The role of the organic cation transporter OCT1. Naunyn Schmiedebergs Arch Pharmacol354: 320–326, 1996.
138.
GrundemannD, SchechingerB, RappoldGA, SchomigE. Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nature Neurosci1: 349–351, 1998.
139.
BuschAE, QuesterS, UlzheimerJC, WaldeggerS, GorboulevV, AmdtP, LangF, KoepsellH. Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1. J Biol Chem271: 32599–32604, 1996.
140.
KoehlerMR, WissingerB, GorboulevV, KoepsellH, SchmidM. The two human organic cation transporter genes SLC22A1 and SLC22A2 are located on chromosome 6q26. Cytogenet Cell Genet79: 198–200, 1997.
141.
KoehlerMR, GorboulevV, KoepsellHM, SteinleinC, SchmidM. Roct1, a rat polyspecific transporter gene for the excretion of cationic drugs, maps to chromosome 1q 11–12. Mamm Genome7: 247–248, 1995.
142.
GorboulevV, VolkC, AmdtP, AkhoundovaA, KoepsellH. Selectivity of the polyspecific cation transporter rOCT1 is changed by mutation of aspartate 475 to glutamate. Mol Pharmacol56: 1254–1261, 1999.
143.
VolkC, GorboulevV, BudimanT, NagelG, KoepsellH. Different affinities of inhibitors to the outwardly and inwardly directed substrate binding site of organic cation transporter 2. Mol Pharmacol64: 1037–1047, 2003.
144.
JonkerJW, WagenaarE, Van EijlS, SchinkelAH. Deficiency in the organic cation transporters 1 and 2 (Oct1/Oct2 [Slc22a1/Slc22a2]) in mice abolishes renal secretion of organic cations. Mol Cell Biol23: 7902–7908, 2003.
145.
JonkerJW, SchinkelAH. Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3). J Pharmacol Exp Ther308: 2–9, 2004.
146.
WuX, GorgeRL, HuangW, WangH, ConwaySJ, LeibachFH, GanapathyV. Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim Biophys Acta1466: 315–327, 2000.
147.
WuX, HuangW, PrasadPD, SethP, RajanDP, LeibachFH, ChenJ, ConwaySJ, GanapathyV. functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/camitine transporter. J Pharmacol Exp Ther290: 1482–1492, 1999.
148.
TraiffortE, RuatM, O'reganS, and MeunierFM. Molecular characterization of the family of choline transporter-like proteins and their variants. J Neurochem92: 1116–1125, 2005.
149.
O'reganS, TraiffortE, RuatM, ChaN, CompaoréD, MeunierF. An electric lobe suppressor for a yeast choline transport mutation belongs to a new family of transporter-like proteins. Proc Natl Acad Sci U S A97: 1835–1840, 2000.
150.
WilleS, SzekeresA, MajdicO, PragerE, StafflerG, StöcklJ, KunthalertD, PrieschlEE, BaumrukerT, BurtscherH, ZlabingerGJ, KnappW, StockingerH. Characterization of CDw92 as a member of the choline transporter-like protein family regulated specifically on dendritic cells. J Immunol167: 5795–5804, 2001.
151.
YuanZ, WagnerL, PoloumienkoA, BakovicM. Identification and expression of a mouse muscle-specific CTL1 gene. Gene341: 305–312, 2004.
152.
MeunierFM, O'reganS. Expression of CTL1 in myelinating structures of Torpedo marmorata. Neuroreport13: 1617–1620, 2002.
153.
YuanZ, TieA, TamopolskiM, BakovicM. Genomic structure, expression and alternative splicing of the human choline transporter like protein. Physiol Genomics (in press), 2005.
154.
InazuM, TakedaH, MatsumiyaT. Molecular and functional characterization of an Na+-independent choline transporter in rat astrocytes. J Neurochem. 94: 1427–1437, 2005.
155.
BishopWR, BellRM. Assembly of phospholipids into cellular membranes: biosynthesis, transmembrane movement and intracellular translocation. Annu Rev Cell Biol4: 579–610, 1988.
156.
O'reganS, MeunierFM. Selection and characterization of the choline transport mutation suppressor from Torpedo electric lobe, CTL1. Neurochem Res28: 551–555, 2003.
157.
ZuffereyR, SantiagoTC, BrachetV, MamounCB. Reexamining the role of choline transporter-like (Ctlp) proteins in choline transport. Neurochem Res29: 461–467, 2004.
158.
FullertonMD, WagnerL, YuanZ, BakovicM. Impaired trafficking of choline transporter like protein-1 at the plasma membrane and inhibition of choline transport in THP-1 monocyte-derived macrophages. Am J Physiol Cell Physiol290: C1230–C1238, 2006.
159.
FujitaT, ShimadaA, OkadaN, YamamotoA. Functional characterization of Na(+)-independent choline transport in primary cultures of neurons from mouse cerebral cortex. Neurosci Lett393: 216–221, 2006.
160.
NovakovaJ, MikasovaL, MachovaE, LisaV, DolezalV. Chronic treatment with amyloid beta(1–42) inhibits non-cholinergic high-affinity choline transport in NG108–15 cells through protein kinase C signaling. Brain Res1062: 101–110, 2005.
161.
LecomteMJ, De GoisS, GuerciA, RavassardP, Faucon BiguetN, MalletJ, BerrudS. Differential expression and regulation of the high-affinity choline transporter CHT1 and choline acetyltransferase in neurons of superior cervical ganglia. Mol Cell Neurosci28: 303–313, 2005.
162.
VissingK, AndersenJL, HarridgeSD, SandriC, HartkoppA, KjaerM, SchjerlingP. Gene expression of myogenic factors and phenotype-specific markers in electrically stimulated muscle of paraplegics. J Appl Physiol99: 164–172, 2005.
163.
MoulyV, AamiriA, BigotA, CooperRN, Di DonnaS, FurlingD, GidaroT, JacqueminV, MamchaouiK, NegroniE, PerieS, RenaultV, Silva-BarbosaSD, Butler-BrowneGS. The mitotic clock in skeletal muscle regeneration, disease and cell mediated gene therapy. Acta Physiol Scand184: 3–15, 2005.
164.
FrenetteJ, ChbinouN, GodboutC, MarsolaisD, FrenettePS. Macrophages, not neutrophils, infiltrate skeletal muscle in mice deficient in P/E selectins after mechanical reloading. Am J Physiol Regul Integr Comp Physiol285: R727–R732, 2003.
