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

J Neurosci. 1999 Aug 1;19(15):6225-34. doi: 10.1523/JNEUROSCI.19-15-06225.1999.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins*
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • DNA Footprinting
  • GABA Plasma Membrane Transport Proteins
  • Glutamate Decarboxylase / genetics*
  • Glutamate Decarboxylase / metabolism
  • Green Fluorescent Proteins
  • Helminth Proteins / physiology*
  • Homeodomain Proteins / classification
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Luminescent Proteins / metabolism
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins*
  • Molecular Sequence Data
  • Mutation / physiology
  • Neurons / metabolism
  • Nuclear Proteins*
  • Organic Anion Transporters*
  • Promoter Regions, Genetic / genetics
  • Transcription, Genetic / physiology*
  • Vesicular Inhibitory Amino Acid Transport Proteins

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • GABA Plasma Membrane Transport Proteins
  • Helminth Proteins
  • Homeodomain Proteins
  • Luminescent Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • Nuclear Proteins
  • Organic Anion Transporters
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • unc-30 protein, C elegans
  • unc-47 protein, C elegans
  • Green Fluorescent Proteins
  • Glutamate Decarboxylase