Chromosomal localization of the human vesicularamine transporter genes

Peter, Doris; Finn, James P.; Klisak, I; Liu, Yongjian; T, Kojis; Heinzmann, C.; Roghani, Ali; Sparkes, Robert S.; Edwards, Robert H.

doi:10.1016/s0888-7543(05)80383-0

Cited by 69 publications

(39 citation statements)

References 16 publications

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“…VMAT2 mediates the intracellular storage of dopamine (and other monoamine neurotransmitters) and serves as another phenotypic marker for midbrain dopamine neurons (20). A number of conditions that change DAT expression do not alter VMAT2, which is thought to provide an excellent index of dopamine cell integrity (10,21).…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers

Bannon

Pruetz

Manning-Bog

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Chronic exposure to cocaine induces long-term adaptations that are likely to involve changes in transcription factor expression. This possibility has not been examined in the cocaine-exposed human brain. The transcription factor nurr1 is highly expressed in rodent midbrain dopamine neurons and is essential for their proper phenotypic development. Here we show that human NURR1 gene expression is robust within control subjects and reduced markedly within the dopamine neurons of human cocaine abusers. NURR1 is known to regulate transcription of the gene encoding the cocainesensitive dopamine transporter (DAT). We show here that DAT gene expression also is reduced markedly in the dopamine neurons of NURR1-deficient cocaine abusers, suggesting that NURR1 plays a critical role in vivo in controlling human DAT gene expression and adaptation to repeated exposure to cocaine.

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Section: Discussionmentioning

confidence: 99%

Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers

Bannon

Pruetz

Manning-Bog

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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“…The human SVMT gene maps to 10q25. 13,14 Takahashi and Uhl 15 clarified the genomic structure of the murine SVMT gene; however, that of human homolog is still unclear.Persico et al 16 examined the TaqI RFLP polymorphism of the SVMT gene 13 for linkage analysis in 16 multiplex pedigrees with schizophrenia spectrum disorders. They obtained results excluding close linkage between the SVMT gene and schizophrenia spectrum disorders in their pedigrees.…”

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confidence: 99%

“…The human SVMT gene maps to 10q25. 13,14 Takahashi and Uhl 15 clarified the genomic structure of the murine SVMT gene; however, that of human homolog is still unclear.…”

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confidence: 99%

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Exon/intron boundaries, novel polymorphisms, and association analysis with schizophrenia of the human synaptic vesicle monoamine transporter (SVMT) gene

et al. 2001

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Keywords: synaptic vesicle monoamine transporter (SVMT); polymorphism; exon/intron boundaries; schizophrenia; association studyThe synaptic vesicular monoamine transporter (SVMT), alternatively vesicular monoamine transporter 2 (VMAT2), pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Altered functions of SVMT have been implicated in the pathogensis of several neuropsychiatric diseases. We determined exon/intron boundaries of the human SVMT gene and performed mutational analysis for the exonic and neighboring intronic regions of the gene. Detected polymorphisms were subject to association analysis with schizophrenia in a familybased design. The human SVMT gene consists, of 16 exons and 15 introns, which is consistent with the murine SVMT gene. When mutational analysis was performed by the single strand conformational polymorphism (SSCP) analysis, we found two and four single nucleotide polymorphisms (SNPs) in exons and neighboring introns, respectively. Neither exonic SNP results in an amino acid change. In family-based association analyses in a sample of 50 Japanese schizophrenics and their parents, no significant association was found for the intronic polymorphisms. Our data suggest that there is no common polymorphism in the SVMT gene affecting the primary structure of the human SVMT protein. Furthermore, we obtained no evidence for the major effect of the novel polymorphisms on susceptibility to schizophrenia. Molecular Psychiatry (2001) 6, 456-460.The synaptic vesicular monoamine transporter (SVMT), alternatively vesicular monoamine transporter 2 (VMAT2), pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles, using the proton gradient maintained across the synaptic vesicular membrane. 1-3 It plays a central role in determining the amount of monoaminergic neurotransmitters packaged in a vesicle to be available for exocytotic release. 4 The transporter is a site of action of important drugs such as reserpine and tetrabenazine, both of which inhibit vesicular amine transport. Reserpine is a useful drug in the treatment of hypertension and schizophrenia; however, high dosages of reserpine frequently produce a syndrome resembling depressive disorder. 5 Several lines of evidence suggest the involvement of the SVMT in the psychostimulant action of amphetamines which induce monoamine efflux from vesicles, 6 resulting in an increased amount of cytoplasmic neurotransmitter, although the mechanism of action remains to be elucidated. The SVMT is also important for sequestering toxins. It modulates susceptibility to N-methyl-4-phenylpyridinium (MPP + ), the active metabolite of the neurotoxin N-methyl-1,2,3,6-tetrahydropyridine (MPTP) that induces Parkinsonism. 7,8 Recent studies on mutant mice lacking the SVMT gene have provided interesting findings. Although homozygotes for the mutated type die shortly after birth, heterozygous mice are viable into adult life and display reduced amphetamine-condition...

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“…Alignment of the bovine, rat, and human vesicular monoamine transporters predicted protein sequences. b-VMATZ = bovine chromaffin cell amine transporter; rVMAT2 = rat 'synaptic vesicle' amine transporter [8]; rVMAT1 = rat 'chromaffin granule' amine transporter [7]; hVMAT2 = human 'synaptic vesicle' amine transporter [25,26]. Identities in the sequence are indicated by periods, differences by the indicated residue, and gaps by hyphens.…”

Section: Tissue Distributionmentioning

confidence: 99%

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

et al. 1994

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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 (VMATZ), than to the rat adrenal counterpart (VMATl). Unlike rat VMATl, bovine VMATZ 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 VMATZ 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, 973%9733].

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Chromosomal localization of the human vesicularamine transporter genes

Cited by 69 publications

References 16 publications

Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers

Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers

Exon/intron boundaries, novel polymorphisms, and association analysis with schizophrenia of the human synaptic vesicle monoamine transporter (SVMT) gene

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

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