PTPsigma promotes retinal neurite outgrowth non-cell-autonomously.
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.
Sajnani
Gustavo
G
Neural Development Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Aricescu
A Radu
AR
Jones
E Yvonne
EY
Gallagher
John
J
Alete
Daniel
D
Stoker
Andrew
A
D000818:Animals; D030161:Avian Proteins / Q000502:physiology*; D002642:Chick Embryo; D002809:Chondroitin Sulfates / Q000494:pharmacology; D004347:Drug Interactions; D005109:Extracellular Matrix / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D016501:Neurites / Q000187:drug effects*; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors
D030161:Avian Proteins; D011993:Recombinant Fusion Proteins; D006493:Heparin; D002809:Chondroitin Sulfates; C516883:PTPRS protein, human; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2