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Identification and characterization of the high-affinity choline transporter

Abstract

In cholinergic neurons, high-affinity choline uptake in presynaptic terminals is the rate-limiting step in acetylcholine synthesis. Using information provided by the Caenorhabditis elegans Genome Project, we cloned a cDNA encoding the high-affinity choline transporter from C. elegans (cho-1). We subsequently used this clone to isolate the corresponding cDNA from rat (CHT1). CHT1 is not homologous to neurotransmitter transporters, but is homologous to members of the Na+-dependent glucose transporter family. Expression of CHT1 mRNA is restricted to cholinergic neurons. The characteristics of CHT1-mediated choline uptake essentially match those of high-affinity choline uptake in rat brain synaptosomes.

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Figure 1: Identification, expression and localization of C. elegans cho-1.
Figure 2: Deduced amino-acid sequence and topological model for the high-affinity choline transporter.
Figure 3: Expression studies of rat CHT1.
Figure 4: Functional expression of rat CHT1 in Xenopus oocytes.
Figure 5: Functional expression of rat CHT1 in COS7 cells.

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Acknowledgements

We thank Y. Iino for the C. elegans N2 strain, Y. Kobayashi for help with basal forebrain preparations, A. Fire for pPD104.53, S. Yamashita for yeast choline-transporter cDNA, T. Suzuki and Y. Kirino for Torpedo electric lobe and its cDNA library, Y. Koyama for laterodorsal tegmental nucleus, K. Kameyama for suggestions and D. Saffen for English corrections. This work was supported by grants from Japan Science and Technology Corporation (CREST) and the Ministry of Japan Society for the Promotion of Science (Research for Future Program).

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Correspondence to Takashi Okuda.

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Okuda, T., Haga, T., Kanai, Y. et al. Identification and characterization of the high-affinity choline transporter. Nat Neurosci 3, 120–125 (2000). https://doi.org/10.1038/72059

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