A human synaptic vesicle monoamine transporter cDNA predicts posttranslational modifications, reveals chromosome 10 gene localization and identifies <i>Taq</i>I RFLPs

Surratt, Christopher K.; Persico, Antonio M.; Xiao, Yang; Edgar, Stephanie R.; Bird, Gary S.; Hawkins, Anita L.; Griffin, Constance A.; Li, Xiang; Jabs, Ethylin Wang; Uhl, George R.

doi:10.1016/0014-5793(93)80539-7

FEBS Letters

1993

DOI: 10.1016/0014-5793(93)80539-7

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A human synaptic vesicle monoamine transporter cDNA predicts posttranslational modifications, reveals chromosome 10 gene localization and identifies TaqI RFLPs

Christopher K. Surratt

Antonio M. Persico

Yang Xiao

et al.

Abstract: A human vesicular monoamine transporter cDNA has been identified by screening a human brainstem library using sequences from the rat brain synaptic vesicle monoamine transporter (SVMT) [(1992) Cell 70,539-551;(1992) Proc. Natl. Acad. Sci. USA 89, 10993-109971. The hSVMT shares 92% amino acid identity with the rat sequence, but displays one less consensus site for asparagine N-linked glycosylation and one more consensus site for phosphorylation by protein kinase C. The human SVMT gene maps to chromosome 10q25 u… Show more

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Cited by 76 publications

(52 citation statements)

References 31 publications

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“…Four of these differential nucleotides result in deduced amino acids different from those reported by Surratt et al 13 There was no evidence for polymorphisms since all chromosomes (20 or more) examined were consistent in our Japanese subjects.…”

contrasting

confidence: 53%

“…Direct sequencing of genomic DNA in our subjects gave rise to some differences in the coding region, compared to the published cDNA sequence, 13 which are described in Figure 1. Four of these differential nucleotides result in deduced amino acids different from those reported by Surratt et al 13 There was no evidence for polymorphisms since all chromosomes (20 or more) examined were consistent in our Japanese subjects.…”

mentioning

confidence: 93%

“…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.…”

mentioning

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.…”

mentioning

confidence: 99%

“…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.…”

mentioning

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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contrasting

confidence: 53%

mentioning

confidence: 93%

mentioning

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.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

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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Exclusion of close linkage between the synaptic vesicular monoamine transporter locus and schizophrenia spectrum disorders

et al. 1995

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The principal brain synaptic vesicular monoamine transporter (VMAT2) is responsible for the reuptake of serotonin, dopamine, norepinephrine, epinephrine, and histamine from the cytoplasm into synaptic vesicles, thus contributing to determination of the size of releasable neurotransmitter vesicular pools. Potential involvement of VMAT2 gene variants in the etiology of schizophrenia and related disorders was tested using polymorphic VMAT2 gene markers in 156 subjects from 16 multiplex pedigrees with schizophrenia, schizophreniform, schizoaffective, and schizotypal disorders and mood incongruent psychotic depression. Assuming genetic homogeneity, complete (theta = 0.0) linkage to the schizophrenia spectrum was excluded under both dominant and recessive models. Allelic variants at the VMAT2 locus do not appear to provide major genetic contributions to the etiology of schizophrenia spectrum disorders in these pedigrees.

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Identification of two risk haplotypes for schizophrenia and bipolar disorder in the synaptic vesicle monoamine transporter gene (SVMT)

Gutiérrez

López-Miguel

Papiol

et al. 2007

American J of Med Genetics Pt B

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The synaptic vesicular monoamine transporter (SVMT) plays a key role in monoaminergic neurotransmission determining the size of neurotransmitter vesicular pools available for exocytotic release. Recently, several lines of evidence have suggested that altered functions of SVMT may be involved in the pathogenesis of certain neuropsychiatric diseases, including psychotic and mood disorders. In the present study, we tested the potential involvement of SVMT gene variants in the etiology of schizophrenia and bipolar disorder. Five different SNPs (T440G, C1368T, T2666C, A2683C, and A745G) were included in the analysis covering a region of about 35 kb along the SVMT gene. Analyses were performed in a case-control sample consisting of 88 bipolar patients, 107 subjects with schizophrenia, and 164 controls. Two risk haplotypes for both schizophrenia and bipolar disorder in SVMT gene were identified. Particularly, 2666T-2683A-745G (TAG) and 2666C-2683C-745A (CCA) combinations were significantly more frequent in both bipolar and schizophrenic patients than in controls. UNPHASED package estimated haplotype effects for all patients yielded relative risks of 4.1 (95%CI: 1.83-9.21) for TAG combination and 2.336 (95%CI: 1.28-4.26) for CCA haplotype. Conversely, 2666T-2683C-745A (TCA) and 2666C-2683A-745G (CAG) haplotypes seemed to protect against these mental disorders, since the estimated frequency in control chromosomes was 12% whilst such haplotypes were not observed in any bipolar or schizophrenic subject (P < 0.0000). Our results strongly suggest that SVMT gene or certain regions of it may constitute a genetic substrate of susceptibility for both schizophrenia and bipolar disorder.

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A human synaptic vesicle monoamine transporter cDNA predicts posttranslational modifications, reveals chromosome 10 gene localization and identifies TaqI RFLPs

Cited by 76 publications

References 31 publications

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

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

Exclusion of close linkage between the synaptic vesicular monoamine transporter locus and schizophrenia spectrum disorders

Identification of two risk haplotypes for schizophrenia and bipolar disorder in the synaptic vesicle monoamine transporter gene (SVMT)

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