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

Torpe, Nanna ; Gopal, Sandeep LU orcid ; Baltaci, Oguzhan ; Rella, Lorenzo ; Handley, Ava ; Korswagen, Hendrik C and Pocock, Roger (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
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.

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author
; ; ; ; ; and
publishing date
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
  • pmid:30893592
  • scopus:85062811345
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
2024-06-01 18:35:03
@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}},
}