Publications

• Stoichiometry of H+-linked dopamine transport in chromaffin granule ghosts.

  Knoth J., Zallakian M., Njus D.

  A proton-translocating adenosinetriphosphatase in adrenal medullary chromaffin granule ghosts can generate either a membrane potential (inside positive) or a pH gradient (inside acid). Dopamine uptake occurs in response to both the membrane potential and the pH gradient. The natural logarithm of t ... >> More

  A proton-translocating adenosinetriphosphatase in adrenal medullary chromaffin granule ghosts can generate either a membrane potential (inside positive) or a pH gradient (inside acid). Dopamine uptake occurs in response to both the membrane potential and the pH gradient. The natural logarithm of the dopamine concentration gradient [In (Din/Dout)] is linearly related to the membrane potential with a slope of F/(RT). This dependence is not affected by the pH of the medium. In (Din/Dout) is linearly dependent on In ([H+]in/[H+]out) with a slope of 2. These results indicate that dopamine is taken up via an exchange diffusion or antiport mechanism. The stoichiometry of this exchange is two H+/dopamine cation and is independent of pH. << Less

  Biochemistry 20:6625-6629(1981) [PubMed] [EuropePMC]

• A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter.

  Liu Y., Peter D., Roghani A., Schuldiner S., Prive G.G., Eisenberg D., Brecha N., Edwards R.H.

  Classical neurotransmitters are transported into synaptic vesicles so that their release can be regulated by neural activity. In addition, the vesicular transport of biogenic amines modulates susceptibility to N-methyl-4-phenylpyridinium (MPP+), the active metabolite of the neurotoxin N-methyl-1,2 ... >> More

  Classical neurotransmitters are transported into synaptic vesicles so that their release can be regulated by neural activity. In addition, the vesicular transport of biogenic amines modulates susceptibility to N-methyl-4-phenylpyridinium (MPP+), the active metabolite of the neurotoxin N-methyl-1,2,3,6-tetrahydropyridine that produces a model of Parkinson's disease. Taking advantage of selection in MPP+, we have used gene transfer followed by plasmid rescue to identify a cDNA clone that encodes a vesicular amine transporter. The sequence predicts a novel mammalian protein with 12 transmembrane domains and homology to a class of bacterial drug resistance transporters. We have detected messenger RNA transcripts for this transporter only in the adrenal gland. Monoamine cell populations in the brain stem express a distinct but highly related protein. << Less

  Cell 70:539-551(1992) [PubMed] [EuropePMC]

• Cloning and functional expression of a tetrabenazine sensitive vesicular monoamine transporter from bovine chromaffin granules.

  Howell M.L., Shirvan A., Stern-Bach Y., Steiner-Mordach S., Dean G.E., Schuldiner S.

  Using oligonucleotide primers derived from the vesicular monoamine transporters sequences, a cDNA predicted to encode the bovine chromaffin granule amine transporter has been cloned (b-VMAT2). Surprisingly, its structure is more similar to the rat brain transporter (VMAT2), than to the rat adrenal ... >> More

  Using oligonucleotide primers derived from the vesicular monoamine transporters sequences, a cDNA predicted to encode the bovine chromaffin granule amine transporter has been cloned (b-VMAT2). Surprisingly, its structure is more similar to the rat brain transporter (VMAT2), than to the rat adrenal counterpart (VMAT1). Unlike rat VMAT1, bovine VMAT2 appears to be expressed both in the adrenal medulla and the brain, as judged by Northern analysis. After modification/deletion of the seven amino acids at the N-terminus of the protein it was expressed in a functional form. The order of affinity of the bovine VMAT2 transporter to substrates is: serotonin > dopamine = norepinephrine > epinephrine. Also, the recombinant bovine adrenal transporter is highly sensitive to tetrabenazine, in sharp contrast to the rat adrenal transporter. The findings indicate, therefore, a clear species variation in which structure and function of the bovine adrenal transporter resemble the rat brain protein, while its tissue distribution is distinct from both types of rat proteins. In addition, the predicted protein sequence is identical to the experimentally determined N-terminus sequence of the purified vesicular amine transporter [Stern-Bach et al. (1992) Proc. Natl. Acad. Sci. USA 89, 9730-9733]. << Less

  FEBS Lett. 338:16-22(1994) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Expression cloning of a reserpine-sensitive vesicular monoamine transporter.

  Erickson J.D., Eiden L.E., Hoffman B.J.

  A cDNA for a rat vesicular monoamine transporter, designated MAT, was isolated by expression cloning in a mammalian cell line (CV-1). The cDNA sequence predicts a protein of 515 amino acids with 12 putative membrane-spanning domains. The characteristics of [3H]serotonin accumulation by CV-1 cells ... >> More

  A cDNA for a rat vesicular monoamine transporter, designated MAT, was isolated by expression cloning in a mammalian cell line (CV-1). The cDNA sequence predicts a protein of 515 amino acids with 12 putative membrane-spanning domains. The characteristics of [3H]serotonin accumulation by CV-1 cells expressing the cDNA clone suggested sequestration by an intracellular compartment. In cells permeabilized with digitonin, uptake was ATP dependent with an apparent Km of 1.3 microM. Uptake was abolished by the proton-translocating ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone and with tri-(n-butyl)tin, an inhibitor of the vacuolar H(+)-ATPase. The rank order of potency to inhibit uptake was reserpine > tetrabenazine > serotonin > dopamine > norepinephrine > epinephrine. Direct comparison of [3H]monoamine uptake indicated that serotonin was the preferred substrate. Photolabeling of membranes prepared from CV-1 cells expressing MAT with 7-azido-8-[125I]iodoketanserin revealed a predominant tetrabenazine-sensitive photolabeled glycoprotein with an apparent molecular mass of approximately 75 kDa. The mRNA that encodes MAT was present specifically in monoamine-containing cells of the locus coeruleus, substantia nigra, and raphe nucleus of rat brain, each of which expresses a unique plasma membrane reuptake transporter. The MAT cDNA clone defines a vesicular monoamine transporter representing a distinct class of neurotransmitter transport molecules. << Less

  Proc. Natl. Acad. Sci. U.S.A. 89:10993-10997(1992) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing.

  Lohoff F.W., Hodge R., Narasimhan S., Nall A., Ferraro T.N., Mickey B.J., Heitzeg M.M., Langenecker S.A., Zubieta J.K., Bogdan R., Nikolova Y.S., Drabant E., Hariri A.R., Bevilacqua L., Goldman D., Doyle G.A.

  Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presyn ... >> More

  Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits and risk for psychopathology. << Less

  Mol. Psychiatry 19:129-139(2014) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• The chromaffin granule and synaptic vesicle amine transporters differ in substrate recognition and sensitivity to inhibitors.

  Peter D., Jimenez J., Liu Y., Kim J., Edwards R.H.

  Classical studies using bovine chromaffin granules have defined the physiologic and pharmacologic properties of the vesicular amine transporter that packages monoamine transmitters into intracellular vesicles for subsequent regulated release. The recent isolation of two distinct but closely relate ... >> More

  Classical studies using bovine chromaffin granules have defined the physiologic and pharmacologic properties of the vesicular amine transporter that packages monoamine transmitters into intracellular vesicles for subsequent regulated release. The recent isolation of two distinct but closely related cDNA clones encoding vesicular amine transport suggests that the activity expressed in the brain (synaptic vesicle amine transporter or SVAT) may differ significantly from the previously described adrenal gland activity (chromaffin granule amine transporter or CGAT). A direct comparison of the two transporters now shows that SVAT has a higher affinity than CGAT for monoamine substrates, in particular for histamine. In addition, SVAT shows approximately 10-fold greater sensitivity to tetrabenazine than CGAT. [3H]Dihydrotetrabenazine shows no detectable binding to CGAT but does bind to SVAT, accounting for the differential sensitivity. Furthermore, methamphetamine preferentially inhibits transport by SVAT relative to CGAT, apparently by competing at the site of amine recognition rather than by disrupting the vesicular pH gradient. These previously unsuspected differences in the storage of monoamine transmitter in the central nervous system and the adrenal gland may help to account for several classic pharmacological observations. << Less

  J. Biol. Chem. 269:7231-7237(1994) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Stoichiometry of catecholamine/proton exchange across the chromaffin-granule membrane.

  Phillips J.H., Apps D.K.

  Catecholamines are accumulated by bovine chromaffin-granule "ghosts" in the presence of MgATP at 25 degrees C. With low concentrations of catecholamine, ratios of internal to external amine concentration of up to 20 000 were obtained. These values fit well with a transport model in which amine acc ... >> More

  Catecholamines are accumulated by bovine chromaffin-granule "ghosts" in the presence of MgATP at 25 degrees C. With low concentrations of catecholamine, ratios of internal to external amine concentration of up to 20 000 were obtained. These values fit well with a transport model in which amine accumulation is both electrogenic and dependent on a pH gradient across the membrane. << Less

  Biochem J 192:273-278(1980) [PubMed] [EuropePMC]