An electric lobe suppressor for a yeast choline transport mutation belongsto a new family of transporter-like proteins

Choline is an important metabolite in all cells due to the major contributi on of phosphatidylcholine to the production of membranes, but it takes on a n added role in cholinergic neurons where it participates in the synthesis of the neurotransmitter acetylcholine. We have cloned a suppressor for a ye ast choline transport mutation from a Torpedo electric lobe yeast expressio n library by functional complementation. The full-length clone encodes a pr otein with 10 putative transmembrane domains, two of which contain transpor ter-like motifs, and whose expression increased high-affinity choline uptak e in mutant yeast. The gene was called CTL1 for its choline transporter-lik e properties. The homologous rat gene, rCTL1, was isolated and found to be highly expressed as a 3.5-kb transcript in the spinal cord and brain and as a 5-kb transcript in the colon. In situ hybridization showed strong expres sion of rCTL1 in motor neurons and oligodendrocytes and to a lesser extent in various neuronal populations throughout the rat brain. High levels of rC TL1 were also identified in the mucosal cell layer of the colon. Although t he sequence of the CTL1 gene shows clear homology with a single gene in Cae norhabditis elegans, several homologous genes are found in mammals (CTL2-4) . These results establish a new family of genes for transporter-like protei ns in eukaryotes and suggest that one of its members, CTL1, is involved in supplying choline to certain cell types, including a specific subset of cho linergic neurons.