Research article

Chibby forms a homodimer through a heptad repeat of leucine residues in its C-terminal coiled-coil motif

Adaobi Mofunanya^1,2 , Feng-Qian Li¹ , Jen-Chih Hsieh^3,4 and Ken-Ichi Takemaru¹

¹  Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York 11794, USA

²  Graduate Program in Genetics, State University of New York at Stony Brook, Stony Brook, New York 11794, USA

³  Department of Biochemistry and Cell Biology, Center for Developmental Genetics, State University of New York at Stony Brook, Stony Brook, New York 11794, USA

⁴  Aderans Research Institute, 3401 Market Street, Philadelphia, Pennsylvania 19104, USA

author email corresponding author email

BMC Molecular Biology 2009, 10:41doi:10.1186/1471-2199-10-41

Published:	12 May 2009

Abstract

Background

The Wnt/β-catenin signaling pathway plays crucial roles in embryonic development and in maintenance of organs and tissues in adults. Chibby (Cby) is an evolutionarily conserved molecule that physically interacts with the key downstream coactivator β-catenin and represses its transcriptional activation potential. Although Cby harbors a predicted coiled-coil motif in the C-terminal region, its molecular nature and functional importance remain largely unexplored.

Results

Here we report that Cby forms a stable complex with itself. Alanine substitutions of two or more of four critical leucine residues within the C-terminal heptad repeats completely eliminate the Cby-Cby interaction. The Cby oligomer predominantly exists as a homodimer. Furthermore, we found that dimerization-deficient Cby mutants still retain the ability to bind to β-catenin and to repress β-catenin-dependent gene activation. More importantly, Cby homodimerization is required for its efficient interaction with the nuclear import receptor importin-α and subsequent nuclear translocation.

Conclusion

Our comprehensive mutational analysis of the Cby coiled-coil domain reveals that the four heptad leucine residues play an essential role in mediating Cby homodimerization. Although monomeric Cby is sufficient to bind to β-catenin and block β-catenin-mediated transcriptional activation, homodimer formation of Cby is indispensable for its efficient nuclear import.