2.50
Hdl Handle:
http://hdl.handle.net/10541/75658
Title:
PTPsigma promotes retinal neurite outgrowth non-cell-autonomously.
Authors:
Sajnani, Gustavo; Aricescu, A Radu; Jones, E Yvonne; Gallagher, John T; Alete, Daniel; Stoker, Andrew
Abstract:
The receptor-like protein tyrosine phosphatase (RPTP) PTPsigma controls the growth and targeting of retinal axons, both in culture and in ovo. Although the principal actions of PTPsigma have been thought to be cell-autonomous, the possibility that RPTPs related to PTPsigma also have non-cell-autonomous signaling functions during axon development has also been supported genetically. Here we report that a cell culture substrate made from purified PTPsigma ectodomains supports retinal neurite outgrowth in cell culture. We show that a receptor for PTPsigma must exist on retinal axons and that binding of PTPsigma to this receptor does not require the known, heparin binding properties of PTPsigma. The neurite-promoting potential of PTPsigma ectodomains requires a basic amino acid domain, previously demonstrated in vitro as being necessary for ligand binding by PTPsigma. Furthermore, we demonstrate that heparin and oligosaccharide derivatives as short as 8mers, can specifically block neurite outgrowth on the PTPsigma substrate, by competing for binding to this same domain. This is the first direct evidence of a non-cell-autonomous, neurite-promoting function of PTPsigma and of a potential role for heparin-related oligosaccharides in modulating neurite promotion by an RPTP.
Affiliation:
Neural Development Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Citation:
PTPsigma promotes retinal neurite outgrowth non-cell-autonomously. 2005, 65 (1):59-71 J. Neurobiol.
Journal:
Journal of Neurobiology
Issue Date:
Oct-2005
URI:
http://hdl.handle.net/10541/75658
DOI:
10.1002/neu.20175
PubMed ID:
16003721
Type:
Article
Language:
en
ISSN:
0022-3034
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorSajnani, Gustavo-
dc.contributor.authorAricescu, A Radu-
dc.contributor.authorJones, E Yvonne-
dc.contributor.authorGallagher, John T-
dc.contributor.authorAlete, Daniel-
dc.contributor.authorStoker, Andrew-
dc.date.accessioned2009-07-24T15:32:36Z-
dc.date.available2009-07-24T15:32:36Z-
dc.date.issued2005-10-
dc.identifier.citationPTPsigma promotes retinal neurite outgrowth non-cell-autonomously. 2005, 65 (1):59-71 J. Neurobiol.en
dc.identifier.issn0022-3034-
dc.identifier.pmid16003721-
dc.identifier.doi10.1002/neu.20175-
dc.identifier.urihttp://hdl.handle.net/10541/75658-
dc.description.abstractThe receptor-like protein tyrosine phosphatase (RPTP) PTPsigma controls the growth and targeting of retinal axons, both in culture and in ovo. Although the principal actions of PTPsigma have been thought to be cell-autonomous, the possibility that RPTPs related to PTPsigma also have non-cell-autonomous signaling functions during axon development has also been supported genetically. Here we report that a cell culture substrate made from purified PTPsigma ectodomains supports retinal neurite outgrowth in cell culture. We show that a receptor for PTPsigma must exist on retinal axons and that binding of PTPsigma to this receptor does not require the known, heparin binding properties of PTPsigma. The neurite-promoting potential of PTPsigma ectodomains requires a basic amino acid domain, previously demonstrated in vitro as being necessary for ligand binding by PTPsigma. Furthermore, we demonstrate that heparin and oligosaccharide derivatives as short as 8mers, can specifically block neurite outgrowth on the PTPsigma substrate, by competing for binding to this same domain. This is the first direct evidence of a non-cell-autonomous, neurite-promoting function of PTPsigma and of a potential role for heparin-related oligosaccharides in modulating neurite promotion by an RPTP.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshAvian Proteins-
dc.subject.meshChick Embryo-
dc.subject.meshChondroitin Sulfates-
dc.subject.meshDrug Interactions-
dc.subject.meshExtracellular Matrix-
dc.subject.meshHeparin-
dc.subject.meshHumans-
dc.subject.meshModels, Biological-
dc.subject.meshNeurites-
dc.subject.meshProtein Binding-
dc.subject.meshProtein Structure, Tertiary-
dc.subject.meshProtein Tyrosine Phosphatases-
dc.subject.meshReceptor-Like Protein Tyrosine Phosphatases, Class 2-
dc.subject.meshRecombinant Fusion Proteins-
dc.subject.meshRetina-
dc.subject.meshRetinal Ganglion Cells-
dc.subject.meshTime Factors-
dc.titlePTPsigma promotes retinal neurite outgrowth non-cell-autonomously.en
dc.typeArticleen
dc.contributor.departmentNeural Development Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.en
dc.identifier.journalJournal of Neurobiologyen
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