Abstract

Neural crest epithelial‐to‐mesenchymal transition (EMT) and migration involves coordinated remodeling of cell‐cell and cell‐matrix adhesions. During this cell phase transition event, interactions between adhesive molecules need to be dynamically regulated. We recently explored the involvement of protein glycosylation in this process. Protein glycosylation is one of the most complexed, yet least studied types of post‐translational modification. By attaching various forms of oligosaccharide (glycan) on different sites of a protein, glycosylation can regulate protein function by modulating its interaction with other molecules. Through the employment of chemical inhibitors for protein glycosylation, we demonstrated that glycosylation is required for neural crest EMT and migration in frog embryos. To gain a comprehensive understanding of how different proteins are glycosylated during this process, we performed a glycoproteomic analysis at different stages of neural crest development. Through this approach, we identified numerous membrane and secreted proteins that are differentially glycosylated, which may contribute to the dynamic changes in cell‐cell and cell‐matrix interactions during neural crest EMT and migration. We focused on E‐cadherin, a well‐known player in EMT and cell migration, to determine the function of specific protein glycosylation in protein activity and consequently in neural crest cell behavior. Our analysis identified two glycosylation linkage sites on E‐cadherin. The two glycosylation sites were mutated individually or in combination, and the function of mutant E‐cadherin was compared with that of wild type E‐cadherin. Our results showed that mutant E‐cadherins were less effective in promoting neural crest cell migration and this was partly due to an increase in the strength of cell‐cell adhesion mediated by the mutan t proteins. Therefore, our findings suggest a new mechanism to fine‐tune the activity of cell adhesive molecules during EMT and migration.Support or Funding InformationNIH R00 DE022796, Georgia Tech Startup Fund

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call