ISSN:
1435-1463
Keywords:
Human
;
rat
;
vesicular monoamine transporter
;
cDNA
;
brain
;
plate-lets
;
MPP+
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary A cDNA encoding the human brain vesicular monoamine transporter (VMT) was isolated and sequenced using PCR. The cDNA contains an open reading frame encoding a hydrophobic polypeptide of 514 amino acids with twelve membrane spanning segments, a calculated molecular weight of 55,709 Da, and an estimated isoelectrical point of 5.62. A structurally identical transporter is expressed in human platelets. Two intraplasmatic consensus phosphorylation sites of cAMP-dependent protein kinase recognition and two potential protein kinase C phosphorylation sites may be central to the regulation of the VMT. Although the human brain VMT is 90.7% homologous to the rat protein, an extensive sequence divergence occurs in the large luminal loop located between the first two transmembrane domains. This loop displays a remarkably reduced homology of 64.0% with several deletions and insertions, although four putative glycosylation sites are conserved. Since functional vesicular monoamine transport supresses MPP+ toxicity and sequence divergence in the large luminal loop of the VMT expressed in rat brain and adrenal medulla may play a role in differential neurotoxic effects of MPP+, our findings indicate one possible molecular basis for the substantial species differences in the suceptibility to MPP+ demonstrated among humans, non-human primates, and rodents. They are also likely to facilitate molecular pharmacologic and genetic investigations of the human VMT in neurodegenerative disorders.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01244941
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