PMID- 7988710 OWN - NLM STAT- MEDLINE DCOM- 19950111 LR - 20190621 IS - 0014-5793 (Print) IS - 0014-5793 (Linking) VI - 356 IP - 1 DP - 1994 Dec 12 TI - Histidine-419 plays a role in energy coupling in the vesicular monoamine transporter from rat. PG - 145-50 AB - Vesicular monoamine transporters (VMAT) catalyze transport of serotonin, dopamine, epinephrine and norepinephrine into subcellular storage organelles in a variety of cells. Accumulation of the neurotransmitter depends on the proton electrochemical gradient across the organelle membrane and involves VMAT-mediated exchange of two lumenal protons with one cytoplasmic amine. It has been suggested in the past that His residues play a role in H+ movement or in its coupling to active transport in H(+)-symporters and antiporters. Indeed VMAT-mediated transport is inhibited by reagents specific for His residues. We have identified one His residue in VMAT1 from rat which is conserved in other vesicular neurotransmitter transporters. Mutagenesis of this His (H419) to either Arg or Cys completely inhibits [3H]serotonin and [3H]dopamine accumulation. Mutagenesis also inhibits other H(+)-dependent partial reactions of VMAT such as the acceleration of binding of the high affinity ligand reserpine, but does not inhibit the [3H]reserpine binding which is not dependent on H+ translocation. It is concluded that His-419 plays a role in energy coupling in r-VMAT1. FAU - Shirvan, A AU - Shirvan A AD - Alexander Silberman Institute of Life Sciences, Hebrew University, Jerusalem, Israel. FAU - Laskar, O AU - Laskar O FAU - Steiner-Mordoch, S AU - Steiner-Mordoch S FAU - Schuldiner, S AU - Schuldiner S LA - eng GR - NS16708/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (Glycoproteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Neuropeptides) RN - 0 (Neurotransmitter Agents) RN - 0 (Slc18a1 protein, rat) RN - 0 (Vesicular Biogenic Amine Transport Proteins) RN - 0 (Vesicular Monoamine Transport Proteins) RN - 333DO1RDJY (Serotonin) RN - 4QD397987E (Histidine) RN - 8B1QWR724A (Reserpine) RN - 94ZLA3W45F (Arginine) RN - K848JZ4886 (Cysteine) SB - IM MH - Animals MH - Arginine/metabolism MH - Biological Transport MH - Cysteine/metabolism MH - Energy Metabolism MH - Glycoproteins/genetics/*metabolism MH - Histidine/*metabolism MH - *Membrane Glycoproteins MH - *Membrane Transport Proteins MH - Mutagenesis, Site-Directed MH - *Neuropeptides MH - Neurotransmitter Agents/genetics/*metabolism MH - Rats MH - Reserpine/metabolism MH - Serotonin/metabolism MH - Vesicular Biogenic Amine Transport Proteins MH - Vesicular Monoamine Transport Proteins EDAT- 1994/12/12 00:00 MHDA- 1994/12/12 00:01 CRDT- 1994/12/12 00:00 PHST- 1994/12/12 00:00 [pubmed] PHST- 1994/12/12 00:01 [medline] PHST- 1994/12/12 00:00 [entrez] AID - 0014-5793(94)01252-0 [pii] AID - 10.1016/0014-5793(94)01252-0 [doi] PST - ppublish SO - FEBS Lett. 1994 Dec 12;356(1):145-50. doi: 10.1016/0014-5793(94)01252-0.