Overview: The high-affinity, hemicholinium-3-sensitive, choline transporter (CHT, provisional nomenclature) is a member of the solute carrier family 5 (SLC5) of sodium-dependent transporters that, in mammals, includes the Na+/substrate co-transporters for glucose, myo-inositol and iodide (Ferguson and Blakely, 2004; Wright and Turk, 2004). CHT contains 13 putative TM domains with an extracellular N-terminus and cytoplasmic C-terminus (Apparsundaram et al., 2000). CHT is expressed mainly in cholinergic neurones on nerve cell terminals and synaptic vesicles (keratinocytes being an additional location). In autonomic neurones, expression of CHT requires an activity-dependent retrograde signal from postsynaptic neurones (Krishnaswamy and Cooper, 2009). Through recapture of choline generated by the hydrolysis of ACh by acetylcholinesterase, CHT serves to maintain ACh synthesis within the presynaptic terminal (Ferguson and Blakely, 2004). Homozygous mice engineered to lack CHT die within one hour of birth as a result of hypoxia arising from failure of transmission at the neuromuscular junction of the skeletal muscles that support respiration (Ferguson et al., 2004). A low-affinity choline uptake mechanism that remains to be identified at the molecular level may involve multiple transporters. In addition, a family of CHT-like proteins with weak Na+ dependence have been described (Traiffort et al., 2005).
| Nomenclature | CHT |
| Other names | CHT1, SLC5A7 |
| Ensembl ID | ENSG00000115665 |
| Endogenous substrates | Choline |
| Selective inhibitors (Ki) | HC-3 (1–5 nM) |
| Probes (KD) | [3H]-HC-3 (4–6 nM) |
| Stoichiometry | 2–3 Na+ : 2–3 Cl- : 1 choline |
Ki and KD values for hemicholinium-3 listed in the table are for human CHT expressed in Xenopus laevis oocytes (Okuda and Haga, 2000), or COS-7 cells (Apparsundaram et al., 2000). Hemicholinium mustard is a substrate for CHT that causes covalent modification and irreversible inactivation of the transporter. Several exogenous substances (e.g. triethylcholine) that are substrates for CHT act as precursors to cholinergic false transmitters.
Glossary
Abbreviations:
- HC-3
hemicholinium-3
Further Reading
Amenta F, Tayebati SK (2008). Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction. Curr Med Chem15: 488–498.
Bazalakova MH, Blakely RD (2006). The high-affinity choline transporter: a critical protein for sustaining cholinergic signaling as revealed in studies of genetically altered mice. Handb Exp Pharmacol175: 525–544.
Ferguson SM, Blakely RD (2004). The choline transporter resurfaces: new roles for synaptic vesicles. Mol Interv4: 22–37.
Okuda T, Haga T (2003). High-affinity choline transporter. Neurochem Res28: 483–488.
Ribeiro FM, Black SA, Prado VF, Rylett RJ, Ferguson SS, Prado MA (2006). The ‘ins’ and ‘outs’ of the high-affinity choline transporter CHT1. J Neurochem97: 1–12.
Sarter M, Parikh V (2005). Choline transporters, cholinergic transmission and cognition. Nat Rev Neurosci6: 48–56.
Wright EM, Turk E (2004). The sodium/glucose cotransport family SLC5. Pflügers Arch447: 510–518.
References
- Apparsundaram S, et al. Biochem Biophys Res Commun. 2000;276:862–867. doi: 10.1006/bbrc.2000.3561. [DOI] [PubMed] [Google Scholar]
- Ferguson SM, et al. Proc Natl Acad Sci USA. 2004;101:8762–8767. doi: 10.1073/pnas.0401667101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krishnaswamy A, Cooper E. Neuron. 2009;61:272–286. doi: 10.1016/j.neuron.2008.11.025. [DOI] [PubMed] [Google Scholar]
- Okuda T, Haga T. FEBS Lett. 2000;484:92–97. doi: 10.1016/s0014-5793(00)02134-7. [DOI] [PubMed] [Google Scholar]
- Traiffort E, et al. J Neurochem. 2005;92:1116–1125. doi: 10.1111/j.1471-4159.2004.02962.x. [DOI] [PubMed] [Google Scholar]