Linked Life Data

18088380

Source:http://linkedlifedata.com/resource/pubmed/id/18088380

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-4-23
pubmed:abstractText
Substrate-induced endocytic trafficking of dopamine transporter (DAT) has been observed, but little is known about the regulation of DAT oligomerization by substrate. The present study investigates the effect on substrates on DAT oligomerization and explores a potential link with the presence of DAT at the cell surface in human embryonic kidney cells transiently or stably expressing N-terminal tagged DAT constructs. Dopamine (100 microM) or amphetamine (2-10 microM) reduced Myc-DAT coimmunoprecipitated along with Flag-DAT (oligomeric DAT) in tandem with a reduction in surface DAT determined by biotinylation. Dopamine (10-1000 microM) and amphetamine (0.2-200 microM) reduced DAT oligomerization as assessed by cross-linking with copper sulfate phenanthroline or Cu2+. Inhibition of endocytosis by 10 microM phenylarsine oxide or 450 mM sucrose counteracted the effect of 10 microM DA or 2 microM amphetamine in reducing DAT cross-linking. In addition to overall similarities between the results with the two cross-linking agents and between the results with the two different endocytosis inhibitors, some differences were noted as well, likely related to the efficiency of the cross-linking process and the sulfhydryl-reactive properties of phenylarsine oxide, respectively. The present results are the first to indicate regulation of oligomerization of an solute carrier family 6 transporter, the DAT, by substrates that act at DAT. In addition, the present study opens up the possibility of an important linkage between oligomerization of DAT and endocytic or other modulatory mechanisms impacting surface DAT.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
910-20
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Substrates dissociate dopamine transporter oligomers.
pubmed:affiliation
Department of Psychiatry, Millhauser Laboratories, New York University School of Medicine, New York 10016, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural