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DIX dynamics

A DIX domain mutant (top) fails to self-aggregate (dots, bottom) or send signals. BIENZ/MACMILLAN

Anew mechanism of signal transduction requires the transducer to rapidly and reversibly build a polymer, report Thomas Schwarz-Romond, Mariann Bienz (MRC Laboratory of Molecular Biology, Cambridge, UK), and colleagues.

The signal transduction protein in question, called Dishevelled (Dvl), is recruited to the plasma membrane when extracellular Wnt ligands bind to cell surface receptors. Dvl forms highly dynamic protein assemblies when overexpressed. Schwarz-Romond et al. now show that the ability to naturally aggregate correlates with Dvl's ability to transduce Wnt signals.

Signaling by Dvl was known to be dependent on a region of the protein called the DIX domain. The team now shows that mutations to this domain also impair homooligomerization.

Electron microscopy and ultracentrifugation revealed that wild-type homooligomers created long fibrils that formed and fell apart in a concentration-dependent manner. The authors suggest that polymerization of Dvl locally concentrates ligand-binding sites to allow efficient interaction with signaling partners, such as the Wnt receptor and Dvl's downstream target, Axin.

Axin is another DIX domain protein that can also self-aggregate. The interaction between Dvl and Axin might be favored by each protein's DIX-dependent polymerization—a theory that the group will explore in the immediate future. Although only three DIX domain proteins are known, the homooligomerizing property is reminiscent of the SAM domain found in certain signaling proteins. Thus, dynamic polymerization might be a more general mechanism of signal transduction.

Reference:

Schwarz-Romond, T., et al. 2007. Nat. Struct. Mol. Biol. doi:10.1038/nsmb1247.[CrossRef][Medline]

Ruth Williams

ruth.williams{at}rockefeller.edu

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This Article Full Text (PDF, 1222K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Williams, R. Search for Related Content PubMed Articles by Williams, R. Social Bookmarking                            What's this?