A Protein Disulfide Isomerase Controls Neuronal Migration through Regulation of Wnt Secretion
(2019) In Cell Reports 26(12). p.5-3190- Abstract
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 EGL20/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.... (More)Appropriate Wnt morphogen secretion is required
(Less)
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 EGL20/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.
- author
- Torpe, Nanna ; Gopal, Sandeep LU ; Baltaci, Oguzhan ; Rella, Lorenzo ; Handley, Ava ; Korswagen, Hendrik C and Pocock, Roger
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Caenorhabditis elegans/cytology, Caenorhabditis elegans Proteins/genetics, Cell Movement, HEK293 Cells, Humans, Neurogenesis, Neurons/cytology, Protein Disulfide-Isomerases/genetics, Wnt Proteins/genetics, Wnt3A Protein/genetics
- in
- Cell Reports
- volume
- 26
- issue
- 12
- pages
- 5 - 3190
- publisher
- Cell Press
- external identifiers
-
- scopus:85062811345
- pmid:30893592
- ISSN
- 2211-1247
- DOI
- 10.1016/j.celrep.2019.02.072
- language
- English
- LU publication?
- no
- additional info
- Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
- id
- adaf78c5-7f43-4465-83ce-a7930052915d
- date added to LUP
- 2021-10-25 13:06:14
- date last changed
- 2024-08-25 02:06:23
@article{adaf78c5-7f43-4465-83ce-a7930052915d, abstract = {{<p>Appropriate Wnt morphogen secretion is required<br> to control animal development and homeostasis.<br> Although correct Wnt globular structure is essential<br> for secretion, proteins that directly mediate Wnt<br> folding and maturation remain uncharacterized.<br> Here, we report that protein disulfide isomerase-1<br> (PDI-1), a protein-folding catalyst and chaperone,<br> controls secretion of the Caenorhabditis elegans<br> Wnt ortholog EGL-20. We find that PDI-1 function is<br> required to correctly form an anteroposterior EGL20/Wnt gradient during embryonic development.<br> Furthermore, PDI-1 performs this role in EGL-20/<br> Wnt-producing epidermal cells to cell-non-autonomously control EGL-20/Wnt-dependent neuronal<br> migration. Using pharmacological inhibition, we<br> further show that PDI function is required in human<br> cells for Wnt3a secretion, revealing a conserved<br> role for disulfide isomerases. Together, these results<br> demonstrate a critical role for PDIs within Wnt-producing cells to control long-range developmental<br> events that are dependent on Wnt secretion.</p>}}, author = {{Torpe, Nanna and Gopal, Sandeep and Baltaci, Oguzhan and Rella, Lorenzo and Handley, Ava and Korswagen, Hendrik C and Pocock, Roger}}, issn = {{2211-1247}}, keywords = {{Animals; Caenorhabditis elegans/cytology; Caenorhabditis elegans Proteins/genetics; Cell Movement; HEK293 Cells; Humans; Neurogenesis; Neurons/cytology; Protein Disulfide-Isomerases/genetics; Wnt Proteins/genetics; Wnt3A Protein/genetics}}, language = {{eng}}, number = {{12}}, pages = {{5--3190}}, publisher = {{Cell Press}}, series = {{Cell Reports}}, title = {{A Protein Disulfide Isomerase Controls Neuronal Migration through Regulation of Wnt Secretion}}, url = {{http://dx.doi.org/10.1016/j.celrep.2019.02.072}}, doi = {{10.1016/j.celrep.2019.02.072}}, volume = {{26}}, year = {{2019}}, }