Abstract:
: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.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Shirvan A,Laskar O,Steiner-Mordoch S,Schuldiner Sdoi
10.1016/0014-5793(94)01252-0subject
Has Abstractpub_date
1994-12-12 00:00:00pages
145-50issue
1eissn
0014-5793issn
1873-3468pii
0014-5793(94)01252-0journal_volume
356pub_type
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