The loading of neurotransmitters into synaptic vesicles

Classical (non-peptide) transmitters are stored into secretory vesicles by a secondary active transporter driven by a V-type H+-ATPase. Five vesicular neurotransmitter uptake activities have been characterized in vitro and, f or three of them, the transporters involved have been identified at the mol ecular level using cDNA cloning and/or Cernorhabditis elegans genetics. The se transporters belong to two protein families, which are both unrelated to the Na+-coupled neurotransmitter transporters operating at the plasma memb rane. The two isoforms of the mammalian vesicular monoamine transporter, VM AT1 and VMAT2, are related to the vesicular acetylcholine transporter (VACH T), while a novel, unrelated vesicular inhibitory amino acid transporter (V IAAT), also designated vesicular GABA transporter (VGAT), is responsible fo r the storage of GABA, glycine or, at some synapses, both amino acids into synaptic vesicles. The observed effects of experimentally altered levels of VACHT or VMAT2 on synaptic transmission and behavior, as well as the recen t awareness that GABAergic or glutamatergic receptors are not always satura ted at central synapses, suggest a potential role of vesicular loading in s ynaptic plasticity. (C) 2000 societe francaise de biochimie et biologie mol eculaire / Editions scientifiques ct medicales Elsevier SAS.