Wormbase gene report for cat-4
cat-4 alleles: e1141, ok342
The gene name cat-4 stands for catecholamine abnormal. The cat-4 mutant was first identified as deficient in the neurotransmitter dopamine by formaldehyde-induced fluorescence (FIF) (Sulston et al., 1975), and subsequently found to be serotonin-deficient by serotonin immunoreactivity (Desai et al., 1988). We and others have also found that cat-4 mutants are hypersensitive to a variety of agents, suggesting they may have a leaky cuticle (Weinshenker et al., 1995; Loer, 1995; Loer, unpublished). At least one report states that cat-4(e1141) mutants possess low levels of serotonin immunoreactivity (Ranganathan et al., 2001)
cat-4 maps genetically between unc-23 and sma-1 on chromosome V. Sequencing through the region identified a candidate gene (F32G8.6) encoding a protein homolgous to the enzyme GTP cyclohydrolase I (GCH1), which catalyzes the first step in biopterin cofactor synthesis (review - free access to complete article). [Biopterin synthesis pathway; GCH enzymatic step] All aromatic amino acid hydroxylase (AAAH) enzymes, which include tryptophan hydroxylase (serotonin synthesis), tyrosine hydroxylase (dopamine synthesis) and phenylalanine hydroxylase (tyrosine synthesis/phenylalanine catabolism), require a biopterin cofactor to catalyze their respective hydroxylations. Mutation in the Drosophila Punch locus, which encodes a GCH1, causes a phenotype similar to that of the cat-4 mutant.
We have found that the F32G8.6 gene in cat-4(e1141) mutants contains a missense mutation that changes an amino acid which is 100% conserved in GCH1 proteins from all known sequences (DePaul & Loer, unpublished). The Gene Knockout Consortium has recently generated a deletion allele of F32G8.6. The homozygous mutant ok342 is serotonin-deficient, and ok342 fails to complement cat-4(e1141) - so is a new, null allele of cat-4.
Published References (unpublished references above are linked to the abstract)
Desai C, Garriga G, McIntire SL, Horvitz HR (1988) A genetic pathway for the development of the Caenorhabditis elegans HSN motor neurons. Nature 336:638-46.
Ranganathan R, Sawin ER, Trent C, Horvitz HR (2001) Mutations in the Caenorhabditis elegans serotonin reuptake transporter mod-5 reveal serotonin-dependent and -independent activities of fluoxetine. J Neurosci 21:58715884.
Sulston J, Dew M, Brenner S (1975) Dopaminergic neurons in the nematode C. elegans. J Comp Neurol 163:215-226.
Weinshenker D, Garriga G, Thomas JH (1995) Genetic and pharmacological analysis of neurotransmitters controlling egg laying in C. elegans. J. Neurosci. 15: 6975-6985.
