Researchers from Development and Regeneration Lab at IBG and their international collaborators have recently published their work on the lipidation of the Wnt3 ligand in zebrafish neural tissues in the journal Frontiers in Cell and Developmental Biology.
Wnt proteins are secreted signaling molecules that play a central role in embryonic development. They are post-translationally lipidated -covalent binding of a lipid group to an aminoacid-; a critical step in their secretion, distribution and function. Initially, Wnts were thought to be dually lipidated at their conserved cysteine and serine residues. However, the results of the high-resolution crystal structure and site-directed mutagenesis analysis have not been very clear on the lipidation sites and their functions.
In this collaborative study, Assoc. Prof. Güneş Özhan and PhD student Yağmur Azbazdar from IBG, as well as their collaborators from the National University of Singapore, showed that lipidation of either one of the cysteine or serine residues was sufficient for secretion and membrane localization of zebrafish Wnt3 in vivo. A double mutant at both residues was neither secreted nor localized on the membrane.
The observations of the research group provide possible explanations of the functional role of the two lipidation sites, with both being sufficient for secretion and membrane localization, serine being necessary for receptor binding and both residues being necessary for signaling.