PMID- 18094261
OWN - NLM
STAT- MEDLINE
DCOM- 20080114
LR  - 20211020
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 27
IP  - 51
DP  - 2007 Dec 19
TI  - Vigorous motor activity in Caenorhabditis elegans requires efficient clearance of 
      dopamine mediated by synaptic localization of the dopamine transporter DAT-1.
PG  - 14216-27
AB  - 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.
FAU - McDonald, Paul W
AU  - McDonald PW
AD  - Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, 
      Tennessee 37232-8548, USA.
FAU - Hardie, Shannon L
AU  - Hardie SL
FAU - Jessen, Tammy N
AU  - Jessen TN
FAU - Carvelli, Lucia
AU  - Carvelli L
FAU - Matthies, Dawn Signor
AU  - Matthies DS
FAU - Blakely, Randy D
AU  - Blakely RD
LA  - eng
GR  - DA014917/DA/NIDA NIH HHS/United States
GR  - MH065782/MH/NIMH NIH HHS/United States
GR  - MH073159/MH/NIMH NIH HHS/United States
GR  - MH58921/MH/NIMH NIH HHS/United States
GR  - NS046237/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Caenorhabditis elegans Proteins)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (SLC6A3 protein, human)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Caenorhabditis elegans
MH  - Caenorhabditis elegans Proteins/analysis/*metabolism
MH  - Cell Line
MH  - Dopamine/*metabolism
MH  - Dopamine Plasma Membrane Transport Proteins/analysis/*metabolism/physiology
MH  - Humans
MH  - Male
MH  - Metabolic Clearance Rate/physiology
MH  - Motor Activity/*physiology
MH  - Synapses/chemistry/*metabolism
PMC - PMC6673513
EDAT- 2007/12/21 09:00
MHDA- 2008/01/15 09:00
PMCR- 2008/06/19
CRDT- 2007/12/21 09:00
PHST- 2007/12/21 09:00 [pubmed]
PHST- 2008/01/15 09:00 [medline]
PHST- 2007/12/21 09:00 [entrez]
PHST- 2008/06/19 00:00 [pmc-release]
AID - 27/51/14216 [pii]
AID - 3301569 [pii]
AID - 10.1523/JNEUROSCI.2992-07.2007 [doi]
PST - ppublish
SO  - J Neurosci. 2007 Dec 19;27(51):14216-27. doi: 10.1523/JNEUROSCI.2992-07.2007.