Abstract
Axin interactor, dorsalization-associated (Aida) was identified as a regulatory factor that utilizes its C-terminal region to interact with axis formation inhibitor (Axin). Aida abrogates the Axin-mediated Jun N-terminal kinase activation required for proper dorsalization during zebrafish embryonic development, and thus functions as a proventralization factor. Here, we report the structure of Aida C-terminal fragments, which adopt a conventional C2 domain topology. We also demonstrate that Aida can specifically bind to phosphoinositides in a Ca2+-independent manner, and is able to associate with the cell membrane via a novel positively charged surface, namely a basic loop. Mutation of the positively charged patch on the basic loop leads to destabilization of the Aida-membrane association or disruption of the Aida-Axin interaction, resulting in impaired Jun N-terminal kinase inhibition. Together, our findings provide a molecular basis for C2 domain-mediated Aida-membrane and Aida-Axin associations.
Original language | English |
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Pages (from-to) | 4622-4632 |
Number of pages | 11 |
Journal | FEBS Journal |
Volume | 281 |
Issue number | 20 |
DOIs | |
Publication status | Published - Oct 2014 |
Externally published | Yes |
Keywords
- Axin interactor
- Axis formation inhibitor (Axin)
- C2 domain
- Dorsalization-associated (Aida)
- Jun N-terminal kinase (JNK)
- Membrane proteins