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Gene Review

dat-1  -  Protein DAT-1

Caenorhabditis elegans

 
 
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Disease relevance of dat-1

  • We demonstrate that agents that interfere with DAT function protect against 6-OHDA toxicity [1].
 

High impact information on dat-1

  • Recently, we have explored the sensitivity of DA neurons in the nematode Caenorhabditis elegans to the Parkinsonian-inducing neurotoxin 6-hydroxydopamine (6-OHDA) and found striking similarities, including DAT dependence, to neurodegeneration observed in mammalian models [2].
  • In this review, we present our findings in the context of molecular and behavioral dimensions of DA signaling in C. elegans with an eye toward opportunities for uncovering DAT mutants, DAT regulators, and components of toxin-mediated cell death [2].
  • The Caenorhabditis elegans gene T23G5.5 encodes an antidepressant- and cocaine-sensitive dopamine transporter [3].
  • Two of the dat-1 alleles derive from point mutations in conserved glycine residues (G55, G90) in contiguous DAT-1 transmembrane domains (TM1 and TM2, respectively), whereas the third allele results in altered translation of the transporter's COOH terminus [4].
  • A genetic screen in Caenorhabditis elegans for dopamine neuron insensitivity to 6-hydroxydopamine identifies dopamine transporter mutants impacting transporter biosynthesis and trafficking [4].
 

Associations of dat-1 with chemical compounds

  • The presynaptic dopamine (DA) transporter (DAT) is a major determinant of synaptic DA inactivation, an important target for psychostimulants including cocaine and amphetamine, and a mediator of DA neuron vulnerability to the neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium ion [4].
  • In the leaves, only diazinon EC, trichlorfon SP, insecticidal soap, oxamyl GR and ZeroTol consistently caused over 70% nematode population reduction compared with the control at 45 DAT in both years [5].
  • Although all twelve chemical pesticides were effective in reducing the population of A fragariae in the soil 45 days after treatment (DAT), only diazinon 475 g liter-1 EC, trichlorfon 800 g kg-1 SP, ethoprophos 100 g kg-1 GR, oxamyl 100 g kg-1 GR and ZeroTol caused over 70% reduction in nematode population compared with the control [5].

References

  1. Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans. Nass, R., Hall, D.H., Miller, D.M., Blakely, R.D. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. The Caenorhabditis elegans dopaminergic system: opportunities for insights into dopamine transport and neurodegeneration. Nass, R., Blakely, R.D. Annu. Rev. Pharmacol. Toxicol. (2003) [Pubmed]
  3. The Caenorhabditis elegans gene T23G5.5 encodes an antidepressant- and cocaine-sensitive dopamine transporter. Jayanthi, L.D., Apparsundaram, S., Malone, M.D., Ward, E., Miller, D.M., Eppler, M., Blakely, R.D. Mol. Pharmacol. (1998) [Pubmed]
  4. A genetic screen in Caenorhabditis elegans for dopamine neuron insensitivity to 6-hydroxydopamine identifies dopamine transporter mutants impacting transporter biosynthesis and trafficking. Nass, R., Hahn, M.K., Jessen, T., McDonald, P.W., Carvelli, L., Blakely, R.D. J. Neurochem. (2005) [Pubmed]
  5. Identification of alternatives for the management of foliar nematodes in floriculture. Jagdale, G.B., Grewal, P.S. Pest Manag. Sci. (2002) [Pubmed]
 
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