Linked Life Data

18094261

Source:http://linkedlifedata.com/resource/pubmed/id/18094261

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
2007-12-20
pubmed:abstractText
The catecholamine dopamine (DA) functions as a powerful modulatory neurotransmitter in both invertebrates and vertebrates. As in man, DA neurons in the nematode Caenorhabditis elegans express a cocaine-sensitive transporter (DAT-1), presumably to regulate synaptic DA signaling and limit DA spillover to extrasynaptic sites, although evidence supporting this is currently lacking. In this report, we describe and validate a novel and readily quantifiable phenotype, swimming-induced paralysis (SWIP) that emerges in DAT-1-deficient nematodes when animals exert maximal physical activity in water. We verify the dependence of SWIP on DA biosynthesis, vesicular packaging, synaptic release, and on the DA receptor DOP-3. Using DAT-1 specific antibodies and GFP::DAT-1 fusions, we demonstrate a synaptic enrichment of DAT-1 that is achieved independently of synaptic targeting of the vesicular monoamine transporter (VMAT). Importantly, dat-1 deletions and point mutations that disrupt DA uptake in cultured C. elegans neurons and/or impact DAT-1 synaptic localization in vivo generate SWIP. SWIP assays, along with in vivo imaging of wild-type and mutant GFP::DAT-1 fusions identify a distal COOH terminal segment of the transporter as essential for efficient somatic export, synaptic localization and in vivo DA clearance. Our studies provide the first description of behavioral perturbations arising from altered trafficking of DATs in vivo in any organism and support a model whereby endogenous DA actions in C. elegans are tightly regulated by synaptic DAT-1.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14216-27
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Vigorous motor activity in Caenorhabditis elegans requires efficient clearance of dopamine mediated by synaptic localization of the dopamine transporter DAT-1.
pubmed:affiliation
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8548, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural