Speer, Kelsey Foss

Email Address
Research Projects
Organizational Units
Research Interests

Search Results

Now showing 1 - 1 of 1
  • Publication
    Investigating The In Vivo Role Of Wnt Acylation
    (2017-01-01) Speer, Kelsey Foss
    Wnts are a family of morphogens that play diverse roles in embryonic patterning, the maintenance of adult stem cells, and the evolution of cancers. Mammalian genomes contain 19 unique Wnt proteins which undergo post-translational acylation at a highly-conserved serine residue. All Wnts bind to the Frizzled (Fz) family of seven-pass transmembrane receptor at an extracellular cysteine-rich domain (CRD). Recent crystallographic evidence suggests that interaction between Wnt and CRD is dependent upon the direct binding of an acyl group on the Wnt to a hydrophobic groove on the CRD. As all vertebrate Wnts are acylated at a conserved site, it is predicted that all Wnts will require acylation to recognize Fzs at the cell surface. However, this hypothesis has not been systematically tested. To address this gap in our understanding, I investigated the role of acylation in the signaling of Wnts in vivo. I hypothesized that if acylation were required for receptor binding, then preventing acylation would abolish the biological activity of these ligands. I tested my hypothesis in Xenopus laevis embryos competent to respond to the ectopic expression of Wnts. Surprisingly, I found that Wnt8 and Wnt3a were capable of robust signaling in vivo even when acylation was prevented. Both ligands also retained the ability to bind to the CRD of Fz8, suggesting that receptor recognition can occur through both acylation-dependent and acylation-independent mechanisms. In contrast, Wnts 1 and 5a required acylation to signal in Xenopus embryos. These findings challenge the assumption that acylation is absolutely required for the biological activity of Wnts. Furthermore, they reveal that Wnts have unique dependencies on acylation for their signaling roles in vivo, which may arise due to unique mechanisms of receptor activation.