Functional characterization of the human high‐affinity choline transporter 1

FEBS Letters

Okuda, Takashi¹  Haga, Tatsuya¹ 

[1] Department of Neurochemistry, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

关键词: High-affinity choline transporter;    Acetylcholine;    CHT1;    high-affinity choline transporter 1;    CHO-1;    high-affinity choline transporter 1 in Caenorhabditis elegans;    HC3;    hemicholinium-3;    GSS;    genomic survey sequence;   

DOI  :  10.1016/S0014-5793(00)02134-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Na⁺-dependent, high-affinity choline uptake in cholinergic neurons is the rate-limiting step in acetylcholine synthesis. Here we report the molecular cloning and functional characterization of the human high-affinity choline transporter (hCHT1). The hCHT1 exhibits significant homology with known members of the Na⁺-dependent glucose transporter family, but not with members of the neurotransmitter transporter family. The human CHT1 gene is 25 kb in length with 9 exons and was assigned to chromosome II at position IIq11–12. Northern blot analysis showed that a 5.4 kb hCHT1 transcript was expressed exclusively in tissues containing cholinergic neurons. When expressed in Xenopus oocytes, the human clone induced Na⁺- and Cl⁻-dependent, high-affinity choline uptake, which was sensitive to the specific inhibitor hemicholinium-3, with a K _i of 1.3 nM. The hCHT1-mediated choline uptake increased with increasing concentrations of choline, Na⁺ and Cl⁻, with EC₅₀ values of 2.0 μM, 76 mM, and 48 mM, and with apparent Hill coefficients of 1, 2.5 and 2.3, respectively.

【 授权许可】

Unknown