| Abstract: | The receptor‐like protein tyrosine phosphatase (RPTP) PTPσ controls the growth and targeting of retinal axons, both in culture and in ovo. Although the principal actions of PTPσ have been thought to be cell‐autonomous, the possibility that RPTPs related to PTPσ 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 PTPσ ectodomains supports retinal neurite outgrowth in cell culture. We show that a receptor for PTPσ must exist on retinal axons and that binding of PTPσ to this receptor does not require the known, heparin binding properties of PTPσ. The neurite‐promoting potential of PTPσ ectodomains requires a basic amino acid domain, previously demonstrated in vitro as being necessary for ligand binding by PTPσ. Furthermore, we demonstrate that heparin and oligosaccharide derivatives as short as 8mers, can specifically block neurite outgrowth on the PTPσ substrate, by competing for binding to this same domain. This is the first direct evidence of a non‐cell‐autonomous, neurite‐promoting function of PTPσ and of a potential role for heparin‐related oligosaccharides in modulating neurite promotion by an RPTP. © 2005 Wiley Periodicals, Inc. J Neurobiol, 2005 |
