RT Journal Article SR Electronic T1 Mapping Netrin Receptor Binding Reveals Domains of Unc5 Regulating Its Tyrosine Phosphorylation JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 10826 OP 10834 DO 10.1523/JNEUROSCI.3715-04.2004 VO 24 IS 48 A1 Robert P. Kruger A1 Jeeyong Lee A1 Weiquan Li A1 Kun-Liang Guan YR 2004 UL http://www.jneurosci.org/content/24/48/10826.abstract AB Netrin and its receptors Unc5 and deleted in colorectal carcinoma (DCC) regulate axon guidance and cell migration. We defined domains involved in the interactions between netrin-1, DCC, and Unc5c. We show that Unc5 requires both Ig domains to interact with netrin. DCC binds through the fourth fibronectin type III domain, whereas netrin binds through multiple domains to both receptors. We examined the functional consequences of removing the netrin binding and nonbinding domains from Unc5 in vitro and in vivo. In human embryonic kidney 293 cells, removal of the netrin binding second Ig domain causes an increase in basal tyrosine phosphorylation, whereas removal of the netrin nonbinding thrombospondin domains decreases tyrosine phosphorylation. Moreover, experiments in Caenorhabditis elegans indicate that both netrin binding and nonbinding domains are necessary for phenotypic rescue of an unc-5 loss of function mutation.