Developmental Expression and Phylogenetic Conservation of Alternatively Spliced Forms of the C-terminal Binding Protein Corepressor

The C-terminal binding protein (CtBP) is an evolutionarily conserved transcriptional corepressor found in multicellular eukaryotes. Multiple forms of the protein are typically found in animal cells, produced from separate genes and by alternative splicing. CtBP isoforms have also been implicated in cytoplasmic functions, including Golgi fission and vesicular trafficking. All forms of CtBP contain a conserved core domain that is homologous to alpha-hydroxyacid dehydrogenases, and a subset of isoforms (CtBP(L)) contain extensions at the C terminus. Despite distinct developmental profiles and knockout phenotypes in the mouse, the properties of different isoforms of the protein are found to be similar in many transcriptional assays. We have investigated the expression and conservation of distinct isoforms of the CtBP protein in insects and found that the expression of multiple, developmentally regulated isoforms is widely conserved. In a variety of Drosophila species, the relative abundance of CtBP(L) to CtBP(S) drops sharply after embryogenesis, revealing a conserved developmental shift. Despite the overall lower levels of this isoform, bioinformatic analysis reveals that exons encoding the C-terminal extension in CtBP(L) are conserved from Diptera to Coleoptera, suggesting that the CtBP(L) isoform contributes an important, evolutionarily conserved function.