Article ; Online: Regulation of nerve growth and patterning by cell surface protein disulphide isomerase.
2020 Volume 9
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 ... ...
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. |
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MeSH term(s) | Animals ; Astrocytes/physiology ; Axon Guidance/physiology ; Cell Line ; Chick Embryo ; Chickens ; Developmental Biology ; Gene Knockdown Techniques ; Growth Cones/physiology ; Humans ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Neurosciences ; Nitric Oxide/metabolism ; Procollagen-Proline Dioxygenase/genetics ; Procollagen-Proline Dioxygenase/metabolism ; Protein Disulfide-Isomerases/genetics ; Protein Disulfide-Isomerases/metabolism ; Rats ; Signal Transduction ; Somites/embryology ; Somites/physiology ; Spinal Nerves/embryology ; Spinal Nerves/physiology |
Chemical Substances | Membrane Proteins ; Nitric Oxide (31C4KY9ESH) ; Procollagen-Proline Dioxygenase (EC 1.14.11.2) ; P4HB protein, human (EC 5.3.4.1) ; Protein Disulfide-Isomerases (EC 5.3.4.1) |
Language | English |
Publishing date | 2020-05-28 |
Publishing country | England |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2687154-3 |
ISSN | 2050-084X ; 2050-084X |
ISSN (online) | 2050-084X |
ISSN | 2050-084X |
DOI | 10.7554/eLife.54612 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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