Coordinated transcriptional regulation of the unc-25 glutamic acid decarboxylase and the unc-47 GABA vesicular transporter by the Caenorhabditis elegans UNC-30 homeodomain protein.
An important aspect of the specification of neuronal fate is the choice of neurotransmitter. In Caenorhabditis elegans the neurotransmitter GABA is synthesized by the UNC-25 glutamic acid decarboxylase (GAD) and packaged into synaptic vesicles by the UNC-47 transporter. Both unc-25 and unc-47 are expressed in 26 GABAergic neurons of five different types. Previously, we have identified that the unc-30 homeobox gene controls the fate of 19 type D GABAergic neurons. We report here that the UNC-30 homeodomain protein transcriptionally regulates the expression of unc-25 and unc-47 in the 19 type D neurons. UNC-30 bound to the unc-25 and unc-47 promoters sequence-specifically. Mutations in the UNC-30 binding sites of the unc-25 and unc-47 promoters abolished the expression of reporter genes in the D neurons. The ectopic expression of UNC-30 induced the ectopic expression of reporter genes driven by the wild-type unc-25 and unc-47 promoters. Our data establish a mechanism for cell type-specific transcriptional coregulation of genes required for the synthesis and packaging of the neurotransmitter GABA.
Department of Biology, Sinsheimer Laboratories, University of California, Santa Cruz, California 95064, USA.
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Eastman
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Horvitz
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D000818:Animals; D001483:Base Sequence / Q000235:genetics; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018983:DNA Footprinting; D050485:GABA Plasma Membrane Transport Proteins; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000378:metabolism; D049452:Green Fluorescent Proteins; D015801:Helminth Proteins / Q000502:physiology*; D018398:Homeodomain Proteins / Q000145:classification / Q000235:genetics / Q000502:physiology*; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins; D027361:Organic Anion Transporters; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D015801:Helminth Proteins; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009687:Nuclear Proteins; D027361:Organic Anion Transporters; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C090946:unc-30 protein, C elegans; C493420:unc-47 protein, C elegans; D049452:Green Fluorescent Proteins; D005968:Glutamate Decarboxylase