Regulation of nerve growth and patterning by cell surface protein disulphide isomerase
- University of Cambridge, United Kingdom
Abstract
Contact repulsion of growing axons is an essential mechanism for spinal nerve patterning. In birds and mammals the embryonic somites generate a linear series of impenetrable barriers, forcing axon growth cones to traverse one half of each somite as they extend towards their body targets. This study shows that protein disulphide isomerase provides a key component of these barriers, mediating contact repulsion at the cell surface in chick half-somites. Repulsion is reduced both in vivo and in vitro by a range of methods that inhibit enzyme activity. The activity is critical in initiating a nitric oxide/S-nitrosylation-dependent signal transduction pathway that regulates the growth cone cytoskeleton. Rat forebrain grey matter extracts contain a similar activity, and the enzyme is expressed at the surface of cultured human astrocytic cells and rat cortical astrocytes. We suggest this system is co-opted in the brain to counteract and regulate aberrant nerve terminal growth.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Medical Research Council
- Geoffrey MW Cook
- Roger J Keynes
Wellcome
- Geoffrey MW Cook
- Roger J Keynes
Spinal Research
- Julia Schaeffer
Trinity College, University of Cambridge
- Roger J Keynes
University of Cambridge
- Geoffrey MW Cook
- Catia Sousa
- Julia Schaeffer
- Katharine Wiles
- Prem Jareonsettasin
- Asanish Kalyanasundaram
- Eleanor Walder
- Catharina Casper
- Serena Patel
- Pei Wei Chua
- Gioia Riboni-Verri
- Mansoor Raza
- Nol Swaddiwudhipong
- Andrew Hui
- Ameer Abdullah
- Saj Wajed
- Roger J Keynes
Rosetrees Trust
- Geoffrey MW Cook
- Julia Schaeffer
- Roger J Keynes
The Anatomical Society
- Eleanor Walder
Amgen Foundation Summer Scholarship
- Gioia Riboni-Verri
The authors declare that the funders provided research equipment and laboratory consumables, as well as salary support for Julia Schaeffer, Eleanor Walder and Gioia Riboni-Verri.
Ethics
Animal experimentation: Chick embryos were used for this work, and all experiments were carried out at earlier developmental stages than those that require ethical approval.
Reviewing Editor
- Carol A Mason, Columbia University, United States
Publication history
- Received: December 19, 2019
- Accepted: May 23, 2020
- Accepted Manuscript published: May 26, 2020 (version 1)
- Accepted Manuscript updated: May 28, 2020 (version 2)
- Version of Record published: June 3, 2020 (version 3)
- Version of Record updated: June 12, 2020 (version 4)
Copyright
© 2020, Cook et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Regulation of nerve growth and patterning by cell surface protein disulphide isomerase
eLife 9:e54612.
https://doi.org/10.7554/eLife.54612
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