1. Regulation of nerve growth and patterning by cell surface protein disulphide isomerase
- Author
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Geoffrey M.W. Cook, Asanish Kalyanasundaram, Roger J. Keynes, Nol Swaddiwudhipong, Katherine Wiles, Prem Jareonsettasin, Catharina Casper, Ameer Abdullah, Saj Wajed, Serena Patel, Julia Schaeffer, Eleanor Walder, Pei Wei Chua, Catia Sousa, Mansoor Raza, Gioia Riboni-Verri, Andrew Hui, Keynes, Roger J [0000-0002-1557-7684], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Cell ,Isomerase ,Chick Embryo ,somite ,0302 clinical medicine ,repeat patterning ,Biology (General) ,Cytoskeleton ,spinal nerve ,0303 health sciences ,Chemistry ,axon guidance ,General Neuroscience ,General Medicine ,Chicken ,3. Good health ,Cell biology ,medicine.anatomical_structure ,Somites ,Gene Knockdown Techniques ,Medicine ,Signal transduction ,Signal Transduction ,Research Article ,Human ,QH301-705.5 ,Science ,Growth Cones ,Procollagen-Proline Dioxygenase ,Protein Disulfide-Isomerases ,Nitric Oxide ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,03 medical and health sciences ,medicine ,Animals ,Humans ,natural sciences ,Growth cone ,030304 developmental biology ,General Immunology and Microbiology ,Neurosciences ,Membrane Proteins ,Embryonic stem cell ,Rats ,Somite ,030104 developmental biology ,Spinal Nerves ,Astrocytes ,Forebrain ,Rat ,Axon guidance ,Developmental biology ,Chickens ,030217 neurology & neurosurgery ,Developmental Biology ,Neuroscience - 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 half-somites. Repulsion is reduced bothin vivoandin vitroby 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.
- Published
- 2020