When Acetylcholine Transporter Goes Awry: The Consequences of VAChT Mutations

Abstract

Vesicular Acetylcholine Transporter (VAChT) is a kind of membrane protein that is usually found in SVs of cholinergic nerve system1. VAChT is 500-amino acid polypeptides consisting of 12 trans-membrane helices (TMs) (Figure 1), with an N-C terminal in the cytosol, and a large N-glycosylated loop between the first and second TMs. It is similar to VMATs (VMAT1 and VMAT2). These two have 60% amino acid similarity and they are 40% identical to VAChT (Figure 2). VAChT protein is coded by the SLC18A3 segment and this segment is expressed by the SLC18 family. SLC18 itself is a member of MFS. VAChT is the part of the drug H+ antiporter-1 family (DHA1, TCID 2.A.1.2)2–4. As for how of its name, VAChT performs the function as an active transporter (Figure 3) for the acetylcholine into the SVs1,4. VAChT expressions also regulate the amount of ACh in the SVs5. It means that the decreased VAChT expression will directly reduce the level of ACh in SVs. VAChT exchanges two protons per substrate molecule with very similar initial velocity kinetics and pH dependencies1. It relates to the activity of VAChT that is able to change tonicity and morphological in SVs6...