Evidence that GRIP, a PDZ-domain protein which is expressed in the embryonic forebrain, co-activates transcription with DLX homeodomain proteins

Brain Res Dev Brain Res. 2001 Oct 24;130(2):217-30. doi: 10.1016/s0165-3806(01)00239-5.

Abstract

The DLX homeodomain proteins control development of the basal ganglia and branchial arches. To identify co-factors that regulate DLX function we utilized the yeast two-hybrid assay, and found a DLX interacting protein (DIP2) which binds to the N-terminal region of DLX2 via a PDZ domain. DIP2 appears to be an alternatively spliced form of GRIP1, a protein known to bind AMPA glutamate receptors via PDZ domains. Thus, we named it GRIP1b. We provide evidence that GRIP1b can function as a transcriptional co-activator of DLX2 and DLX5. Glutamate receptors inhibit this co-activation. These results suggest that some PDZ proteins may regulate transcription via their interactions with homeodomain proteins. Furthermore, these results suggest a link between glutamate receptors, PDZ proteins and the DLX transcription factors, all of which are co-expressed in the developing basal ganglia.

Publication types

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

MeSH terms

  • Alternative Splicing / physiology
  • Animals
  • Arabidopsis Proteins*
  • Basal Ganglia / embryology*
  • Basal Ganglia / physiology*
  • Cytoskeletal Proteins
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Enhancer Elements, Genetic / physiology
  • Fungal Proteins / genetics
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Mice
  • Nuclear Receptor Coactivator 2
  • Protein Structure, Tertiary
  • RNA-Binding Proteins
  • Receptors, AMPA / genetics
  • Saccharomyces cerevisiae Proteins*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptional Activation / physiology
  • Two-Hybrid System Techniques
  • Yeasts

Substances

  • Arabidopsis Proteins
  • Cytoskeletal Proteins
  • DIP2 protein, Arabidopsis
  • DNA-Binding Proteins
  • Distal-less homeobox proteins
  • Dlx5 protein, mouse
  • Dlx6 protein, mouse
  • Fungal Proteins
  • GAL4 protein, S cerevisiae
  • Homeodomain Proteins
  • Ncoa2 protein, mouse
  • Nuclear Receptor Coactivator 2
  • RNA-Binding Proteins
  • Receptors, AMPA
  • Saccharomyces cerevisiae Proteins
  • Tes protein, mouse
  • Transcription Factors
  • glutamate receptor ionotropic, AMPA 3
  • glutamate receptor ionotropic, AMPA 2