title: Biochemistry and molecular biology of the vesicular monoamine transporter from chromaffin granules.
abstract: Prior to secretion, monoamines (catecholamines, serotonin, histamine) are concentrated from the cytoplasm into vesicles by vesicular monoamine transporters (VMAT). These transporters also carry non-physiological compounds, e.g. the neurotoxin methyl-4-phenylpyridinium. VMAT acts as an electrogenic antiporter (exchanger) of protons and monoamines, using a proton electrochemical gradient. Vesicular transport is inhibited by specific ligands, including tetrabenazine, ketanserin and reserpine. The mechanism of transport and the biochemistry of VMAT have been analyzed with the help of these tools, using mainly the chromaffin granules from bovine adrenal glands as a source of transporter. Although biochemical studies did not suggest a multiplicity of VMATs, two homologous but distinct VMAT genes have recently been cloned from rat, bovine and human adrenal glands. The VMAT proteins are predicted to possess 12 transmembrane segments, with both extremities lying on the cytoplasmic side. They possess N-glycosylation sites in a putative luminal loop and phosphorylation sites in cytoplasmic domains. In rat, VMAT1 is expressed in the adrenal gland whereas VMAT2 is expressed in the brain. In contrast, we found that the bovine adrenal gland expressed both VMAT1 and VMAT2. VMAT2 corresponds to the major transporter of chromaffin granules, as shown by partial peptidic sequences of the purified protein and by a pharmacological analysis of the transport obtained in transfected COS cells (COS cells are monkey kidney cells possessing the ability to replicate SV-40-origin-containing plasmids). We discuss the possibility that VMAT1 may be specifically addressed to large secretory granules vesicles, whereas VMAT2 may also be addressed to small synaptic vesicles; species differences would then reflect the distinct physiological roles of the small synaptic vesicles in the adrenal gland.
authors: CNRS URA 1112, Neurobiologie Physico-Chimique, Institut de Biologie Physico-Chimique, Paris, France.
authors: J P
authors: JP
authors: Henry
authors: D
authors: D
authors: Botton
authors: C
authors: C
authors: Sagne
authors: M F
authors: MF
authors: Isambert
authors: C
authors: C
authors: Desnos
authors: V
authors: V
authors: Blanchard
authors: R
authors: R
authors: Raisman-Vozari
authors: E
authors: E
authors: Krejci
authors: J
authors: J
authors: Massoulie
authors: B
authors: B
authors: Gasnier
mesh_terms: D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D002837:Chromaffin Granules / Q000378:metabolism*; D015870:Gene Expression; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007668:Kidney; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D014162:Transfection; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
chemical_list: D006023:Glycoproteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; C493449:SLC18A1 protein, human; C493452:SLC18A2 protein, human; C493451:Slc18a1 protein, rat; C493454:Slc18a2 protein, rat; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins