A Protein Disulfide Isomerase Controls Neuronal Migration through Regulation of Wnt Secretion

Publication date: 19 March 2019Source: Cell Reports, Volume 26, Issue 12Author(s): Nanna Torpe, Sandeep Gopal, Oguzhan Baltaci, Lorenzo Rella, Ava Handley, Hendrik C. Korswagen, Roger PocockSummaryAppropriate Wnt morphogen secretion is required to control animal development and homeostasis. Although correct Wnt globular structure is essential for secretion, proteins that directly mediate Wnt folding and maturation remain uncharacterized. Here, we report that protein disulfide isomerase-1 (PDI-1), a protein-folding catalyst and chaperone, controls secretion of the Caenorhabditis elegans Wnt ortholog EGL-20. We find that PDI-1 function is required to correctly form an anteroposterior EGL-20/Wnt gradient during embryonic development. Furthermore, PDI-1 performs this role in EGL-20/Wnt-producing epidermal cells to cell-non-autonomously control EGL-20/Wnt-dependent neuronal migration. Using pharmacological inhibition, we further show that PDI function is required in human cells for Wnt3a secretion, revealing a conserved role for disulfide isomerases. Together, these results demonstrate a critical role for PDIs within Wnt-producing cells to control long-range developmental events that are dependent on Wnt secretion.Graphical Abstract

Source: Cell Reports - March 20, 2019 Category: Cytology Source Type: research