Molecular properties of the high-affinity choline transporter CHT1

This article summarizes molecular properties of the high-affinity choline transporter (CHT1) with reference to the historical background focusing studies performed in laboratories of the author. CHT1 is present on the presynaptic terminal of cholinergic neurons, and takes up choline which is the precursor of acetylcholine. The Na(+)-dependent uptake of choline by CHT1 is the rate-limiting step for synthesis of acetylcholine. CHT1 is the integral membrane protein with 13 transmembrane segments, belongs to the Na(+)/glucose co-transporter family (SLC5), and has 20-25% homology with members of this family. A single nucleotide polymorphism (SNP) for human CHT1 has been identified, which has a replacement from isoleucine to valine in the third transmembrane segment and shows the choline uptake activity of 50-60% as much as that of wild-type CHT1. The proportion of this SNP is high among Asians. Possible importance of choline diet for those with this SNP was discussed.