High-affinity choline transporter 1 (CHT1) (CHT1)

High-affinity choline transporter 1 (CHT1), encoded by the SLC5A7 gene, is a transmembrane protein that functions as the rate-limiting step in the synthesis of the neurotransmitter acetylcholine (ACh) [PMID: 21156154]. It is primarily localized in the presynaptic terminals of cholinergic neurons, where it transports extracellular choline into the cytoplasm in a sodium- and chloride-dependent manner [UniProt: P48067]. This process is essential for maintaining ACh levels during periods of high neuronal activity, as the pool of available choline is rapidly depleted without efficient reuptake [PMID: 30243591]. Dysregulation or genetic mutations in CHT1 are associated with several pathologies, including congenital myasthenic syndrome type 20 and distal hereditary motor neuronopathy type VIIB [NCBI Gene: 55676]. In Alzheimer's disease, a decrease in CHT1 expression and function contributes to the cholinergic deficit observed in patients [PMID: 24639474]. Consequently, CHT1 is a significant target for therapeutic intervention, with research focusing on enhancers like coluracetam to improve cognitive function and PET tracers like [18F]FEOBV to map cholinergic denervation [PMID: 8740014, PMID: 24639474].

Other names

SLC5A7Solute carrier family 5 member 7Hemicholinium-3-sensitive choline transporterHACUCHTCholine transporters

Facilitates the sodium- and chloride-dependent reuptake of extracellular choline into presynaptic cholinergic neurons, serving as the rate-limiting step for acetylcholine synthesis [UniProt: P48067, PMID: 21156154].