The Choline Transporter Resurfaces: New Roles for Synaptic Vesicles?

CHT supports presynaptic ACh synthesis. (A) Molecular structures for choline, the substrate of CHT, the neurotransmitter acetylcholine (ACh), and hemicholinium-3 (HC-3), a selective, high-affinity CHT antagonist. (B) At cholinergic presynaptic terminals, CHT functions at the plasma membrane to transport choline into the cytoplasm where it is efficiently acetylated by choline acetyltransferase (ChAT) to generate acetylcholine (ACh). This ACh is packaged into synaptic vesicles by the vesicular acetylcholine transporter (VAChT), a second cholinergic neuron specific transporter. Upon neuron stimulation, ACh-containing vesicles fuse with the plasma membrane in response to elevated cytoplasmic [Ca²⁺ ]. Within the synaptic cleft, ACh is inactivated by acetylcholinesterase- (AChE)-mediated hydrolysis, and the recapture of choline by CHT is the rate-limiting step in subsequent ACh synthesis.