TY - JOUR
T1 - A Protein Disulfide Isomerase Controls Neuronal Migration through Regulation of Wnt Secretion
AU - Torpe, Nanna
AU - Gopal, Sandeep
AU - Baltaci, Oguzhan
AU - Rella, Lorenzo
AU - Handley, Ava
AU - Korswagen, Hendrik C.
AU - Pocock, Roger
N1 - Funding Information:
We thank members of the Pocock Laboratory and Brent Neumann for comments on the manuscript. Some strains were provided by the Caenorhabditis Genetics Center (University of Minnesota), which is funded by NIH Office of Research Infrastructure Programs ( P40 OD010440 ). This work was supported by the following grants: Monash University Senior Postdoctoral Fellowship to S.G., NWO-ALW (Open Program Grant 822.02.012 ) to H.C.K., European Research Council (ERC Starting Grant 260807 to R.P.), Lundbeck Foundation (Project R67-A6094 to R.P.), NHMRC (Project GNT1105374 and Senior Research Fellowship GNT1137645 to R.P.), and veski innovation fellowship ( VIF23 to R.P.).
Funding Information:
We thank members of the Pocock Laboratory and Brent Neumann for comments on the manuscript. Some strains were provided by the Caenorhabditis Genetics Center (University of Minnesota), which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). This work was supported by the following grants: Monash University Senior Postdoctoral Fellowship to S.G., NWO-ALW (Open Program Grant 822.02.012) to H.C.K., European Research Council (ERC Starting Grant 260807 to R.P.), Lundbeck Foundation (Project R67-A6094 to R.P.), NHMRC (Project GNT1105374 and Senior Research Fellowship GNT1137645 to R.P.), and veski innovation fellowship (VIF23 to R.P.).
Publisher Copyright:
© 2019 The Author(s)
PY - 2019/3/19
Y1 - 2019/3/19
N2 - Appropriate 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.
AB - Appropriate 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.
KW - neuronal migration
KW - protein disulfide isomerase
KW - Wnt morphogen
KW - Wnt secretion
UR - https://www.scopus.com/pages/publications/85062811345
U2 - 10.1016/j.celrep.2019.02.072
DO - 10.1016/j.celrep.2019.02.072
M3 - Article
C2 - 30893592
AN - SCOPUS:85062811345
SN - 2211-1247
VL - 26
SP - 3183-3190.e5
JO - Cell Reports
JF - Cell Reports
IS - 12
ER -