PrP and its Ancestral Relatives ZIP6 and ZIP10 Interact with NCAM1, Altering its Molecular Environment and Post-translational Modifications during Epithelial-to-mesenchymal Transition

The prion protein (PrP) was recently found to be evolutionarily linked to a subfamily of ZIP transporters which possess a PrP-like domain. A member of this subfamily, ZIP6, is of particular interest as separate studies have shown that morpholino knockdowns of ZIP6 or PrP in zebrafish leads to an impairment in gastrulation, a process dependent on epithelial-to-mesenchymal transition (EMT). Furthermore, the neural cell adhesion molecule (NCAM1), a known interactor of PrP, has itself been described as a mediator of EMT. Based on these findings, we hypothesized that both PrP and ZIP6 play crucial roles in the process of EMT by controlling the environment surrounding NCAM. We determined that ZIP6 forms a heteromeric complex with ZIP10 that affects NCAM1â s integration into adhesion complexes while also mediating its phosphorylation during EMT. Meanwhile, PrP was found to have a unique role in controlling the polysialylation of NCAM1 during EMT.M.Sc.2017-11-21 00:00:0