PTPsigma promotes retinal neurite outgrowth non-cell-autonomously.
Sajnani, Gustavo ; Aricescu, A Radu ; Jones, E Yvonne ; Gallagher, John T ; Alete, Daniel ; Stoker, Andrew
Sajnani, Gustavo
Aricescu, A Radu
Jones, E Yvonne
Gallagher, John T
Alete, Daniel
Stoker, Andrew
Citations
Altmetric:
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.
Description
Date
2005-10
Publisher
Collections
Keywords
Type
Article
Citation
PTPsigma promotes retinal neurite outgrowth non-cell-autonomously. 2005, 65 (1):59-71 J. Neurobiol.