The level of DLDB/CHIP controls the activity of the LIM homeodomain protein apterous: evidence for a functional tetramer complex in vivo

EMBO J. 2000 Jun 1;19(11):2602-14. doi: 10.1093/emboj/19.11.2602.


The LIM homeodomain (LIM-HD) protein Apterous (Ap) and its cofactor DLDB/CHIP control dorso- ventral (D/V) patterning and growth of Drosophila wing. To investigate the molecular mechanisms of Ap/CHIP function we altered their relative levels of expression and generated mutants in the LIM1, LIM2 and HD domains of Ap, as well as in the LIM-interacting and self-association domains of CHIP. Using in vitro and in vivo assays we found that: (i) the levels of CHIP relative to Ap control D/V patterning; (ii) the LIM1 and LIM2 domains differ in their contributions to Ap function; (iii) Ap HD mutations cause weak dominant negative effects; (iv) overexpression of ChipDeltaSAD mutants mimics Ap lack-of-function, and this dominant negative phenotype is caused by titration of Ap because it can be rescued by adding extra Ap; and (v) overexpression of ChipDeltaLID mutants also causes an Ap lack-of-function phenotype, but it cannot be rescued by extra Ap. These results support the model that the Ap-CHIP active complex in vivo is a tetramer.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • Dimerization
  • Drosophila Proteins*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism*
  • Gene Expression Regulation, Developmental*
  • Genes, Homeobox
  • Genes, Reporter
  • Genetic Complementation Test
  • Homeodomain Proteins*
  • Insect Proteins / genetics
  • Insect Proteins / physiology*
  • LIM-Homeodomain Proteins
  • Macromolecular Substances
  • Morphogenesis / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Phenotype
  • Protein Conformation
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Wings, Animal / growth & development


  • Chi protein, Drosophila
  • Drosophila Proteins
  • Homeodomain Proteins
  • Insect Proteins
  • LIM-Homeodomain Proteins
  • Macromolecular Substances
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Transcription Factors
  • ap protein, Drosophila