Members of the choline transporter-like family are encoded by five genes (CTL1-CTL5) with further diversity occurring through alternative splicing of CTL1, 4 and 5 [9]. CTL family members are putative 10TM domain proteins with extracellular termini that mediate Na⁺-independent transport of choline with an affinity that is intermediate to that of the high affinity choline transporter CHT1 (SLC5A7) and the low affinity organic-cation transporters [OCT1 (SLC22A1) and OCT2 (SLC22A2)] [6]. CLT1 is expressed almost ubiquitously in human tissues [11] and mediates choline transport across the plasma and mitochondrial membranes [5]. Transport of choline by CTL2, which in rodents is expressed as two isoforms (CTL2P1 and CLTP2; [3]) in lung, colon, inner ear and spleen and to a lesser extent in brain, tongue, liver, and kidney, has only recently been demonstrated [3,8]. CTL3-5 remain to be characterized functionally.

Data tabulated are features observed for CLT1 endogenous to: rat astrocytes [2]; rat renal tubule epithelial cells [12]; human colon carcinoma cells [4]; human keratinocytes [10] and human neuroblastoma cells [13]. Choline uptake by CLT1 is inhibited by numerous organic cations (e.g. [2,12-13]). In the guinea-pig, CTL2 is a target for antibody-induced hearing loss [7] and in man, a polymorphism in CTL2 constitutes the human neutrophil alloantigen-3a (HNA-3a; [1]).

* Key recommended reading is highlighted with an asterisk

* Inazu M. (2014) Choline transporter-like proteins CTLs/SLC44 family as a novel molecular target for cancer therapy. Biopharm Drug Dispos, 35 (8): 431-49. [PMID:24532461]

Lockman PR, Allen DD. (2002) The transport of choline. Drug Dev Ind Pharm, 28 (7): 749-71. [PMID:12236062]

Michel V, Yuan Z, Ramsubir S, Bakovic M. (2006) Choline transport for phospholipid synthesis. Exp Biol Med (Maywood), 231 (5): 490-504. [PMID:16636297]

* Traiffort E, O'Regan S, Ruat M. (2013) The choline transporter-like family SLC44: properties and roles in human diseases. Mol Aspects Med, 34 (2-3): 646-54. [PMID:23506897]

1. Greinacher A, Wesche J, Hammer E, Fürll B, Völker U, Reil A, Bux J. (2010) Characterization of the human neutrophil alloantigen-3a. Nat Med, 16 (1): 45-8. [PMID:20037594]

2. Inazu M, Takeda H, Matsumiya T. (2005) Molecular and functional characterization of an Na+-independent choline transporter in rat astrocytes. J Neurochem, 94 (5): 1427-37. [PMID:16000150]

3. Kommareddi PK, Nair TS, Thang LV, Galano MM, Babu E, Ganapathy V, Kanazawa T, McHugh JB, Carey TE. (2010) Isoforms, expression, glycosylation, and tissue distribution of CTL2/SLC44A2. Protein J, 29 (6): 417-26. [PMID:20665236]

4. Kouji H, Inazu M, Yamada T, Tajima H, Aoki T, Matsumiya T. (2009) Molecular and functional characterization of choline transporter in human colon carcinoma HT-29 cells. Arch Biochem Biophys, 483 (1): 90-8. [PMID:19135976]

5. Michel V, Bakovic M. (2009) The solute carrier 44A1 is a mitochondrial protein and mediates choline transport. FASEB J, 23 (8): 2749-58. [PMID:19357133]

6. Michel V, Yuan Z, Ramsubir S, Bakovic M. (2006) Choline transport for phospholipid synthesis. Exp Biol Med (Maywood), 231 (5): 490-504. [PMID:16636297]

7. Nair TS, Kozma KE, Hoefling NL, Kommareddi PK, Ueda Y, Gong TW, Lomax MI, Lansford CD, Telian SA, Satar B et al.. (2004) Identification and characterization of choline transporter-like protein 2, an inner ear glycoprotein of 68 and 72 kDa that is the target of antibody-induced hearing loss. J Neurosci, 24 (7): 1772-9. [PMID:14973250]

8. Nakamura T, Fujiwara R, Ishiguro N, Oyabu M, Nakanishi T, Shirasaka Y, Maeda T, Tamai I. (2010) Involvement of choline transporter-like proteins, CTL1 and CTL2, in glucocorticoid-induced acceleration of phosphatidylcholine synthesis via increased choline uptake. Biol Pharm Bull, 33 (4): 691-6. [PMID:20410607]

9. Traiffort E, Ruat M, O'Regan S, Meunier FM. (2005) Molecular characterization of the family of choline transporter-like proteins and their splice variants. J Neurochem, 92 (5): 1116-25. [PMID:15715662]

10. Uchida Y, Inazu M, Takeda H, Yamada T, Tajima H, Matsumiya T. (2009) Expression and functional characterization of choline transporter in human keratinocytes. J Pharmacol Sci, 109 (1): 102-9. [PMID:19122366]

11. Wille S, Szekeres A, Majdic O, Prager E, Staffler G, Stöckl J, Kunthalert D, Prieschl EE, Baumruker T, Burtscher H et al.. (2001) Characterization of CDw92 as a member of the choline transporter-like protein family regulated specifically on dendritic cells. J Immunol, 167 (10): 5795-804. [PMID:11698453]

12. Yabuki M, Inazu M, Yamada T, Tajima H, Matsumiya T. (2009) Molecular and functional characterization of choline transporter in rat renal tubule epithelial NRK-52E cells. Arch Biochem Biophys, 485 (1): 88-96. [PMID:19236841]

13. Yamada T, Inazu M, Tajima H, Matsumiya T. (2011) Functional expression of choline transporter-like protein 1 (CTL1) in human neuroblastoma cells and its link to acetylcholine synthesis. Neurochem Int, 58 (3): 354-65. [PMID:21185344]