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Gene Review

unc-17  -  UNCoordinated

Caenorhabditis elegans

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Disease relevance of unc-17

  • Mutations in unc-17 protect against organophosphorus toxicity, indicating a role in cholinergic neurotransmission [1].
 

High impact information on unc-17

  • The Caenorhabditis elegans unc-17 gene: a putative vesicular acetylcholine transporter [2].
  • On the basis of sequence similarity to mammalian vesicular transporters of biogenic amines and of localization to synaptic vesicles of cholinergic neurons in C. elegans, unc-17 likely encodes the vesicular transporter of acetylcholine [2].
  • Using the relationship of the Torpedo sequence to unc-17, we then isolated the cDNA for a rat homologue (rVAChT) [1].
  • Sequence analysis of cDNAs predicts a protein of 71.5 kDa; comparison of the deduced amino acid sequence with ChAT sequences from other species confirms that cha-1 encodes ChAT [3].
  • We have determined the sites of four transposon insertions and the end-points of two deletions that lead to the cha-1 mutant phenotype; one of the deletions appears to eliminate gene function completely [3].
 

Biological context of unc-17

 

Associations of unc-17 with chemical compounds

  • Mutations that eliminated all unc-17 gene function were lethal, suggesting that the acetylcholine transporter is essential [2].
  • In C. elegans, the gene cha-1 is the structural gene for choline acetyltransferase, the enzyme which synthesizes acetylcholine. cha-1 is a complex gene which includes the previously described unc-17 locus; it has been hypothesized that a single protein is encoded which consists of several discrete structural domains [6].
 

Other interactions of unc-17

  • The segregation of the closely linked flanking markers, unc-17 and unc-5, revealed whether the lethal mutation was to the left or the right of m118 [7].
  • The remaining three mutants (unc-4, cha-1, and unc-17) are defective for synthesis or packaging of acetylcholine in the VCs [8].

References

  1. Molecular cloning of a putative vesicular transporter for acetylcholine. Roghani, A., Feldman, J., Kohan, S.A., Shirzadi, A., Gundersen, C.B., Brecha, N., Edwards, R.H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  2. The Caenorhabditis elegans unc-17 gene: a putative vesicular acetylcholine transporter. Alfonso, A., Grundahl, K., Duerr, J.S., Han, H.P., Rand, J.B. Science (1993) [Pubmed]
  3. Cloning and characterization of the choline acetyltransferase structural gene (cha-1) from C. elegans. Alfonso, A., Grundahl, K., McManus, J.R., Rand, J.B. J. Neurosci. (1994) [Pubmed]
  4. Analysis of point mutants in the Caenorhabditis elegans vesicular acetylcholine transporter reveals domains involved in substrate translocation. Zhu, H., Duerr, J.S., Varoqui, H., McManus, J.R., Rand, J.B., Erickson, J.D. J. Biol. Chem. (2001) [Pubmed]
  5. Alternative splicing leads to two cholinergic proteins in Caenorhabditis elegans. Alfonso, A., Grundahl, K., McManus, J.R., Asbury, J.M., Rand, J.B. J. Mol. Biol. (1994) [Pubmed]
  6. Genetic analysis of the cha-1-unc-17 gene complex in Caenorhabditis. Rand, J.B. Genetics (1989) [Pubmed]
  7. Fine-structure genetics of ama-1, an essential gene encoding the amanitin-binding subunit of RNA polymerase II in Caenorhabditis elegans. Bullerjahn, A.M., Riddle, D.L. Genetics (1988) [Pubmed]
  8. Genetic and cellular basis for acetylcholine inhibition of Caenorhabditis elegans egg-laying behavior. Bany, I.A., Dong, M.Q., Koelle, M.R. J. Neurosci. (2003) [Pubmed]
 
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