RT Journal Article
SR Electronic
T1 Identification of Domains of Netrin UNC-6 that Mediate Attractive and Repulsive Guidance and Responses from Cells and Growth Cones
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7080
OP 7087
DO 10.1523/JNEUROSCI.22-16-07080.2002
VO 22
IS 16
A1 Lim, Yoo-shick
A1 Wadsworth, William G.
YR 2002
UL http://www.jneurosci.org/content/22/16/7080.abstract
AB Netrin UNC-6 is a protein secreted from ventral cells that guides cell and growth cone migrations in Caenorhabditis elegans. Previously it was shown that UNC-6 domain V-2 regulates dorsal guidance activity and domain C regulates an activity that prevents the branching of axons when they respond to the N-terminal domains. Because these results indicate that the biological activities of UNC-6 are mediated through specific domains, we systematically examined each UNC-6 domain for guidance activities. Transgenic animals expressing UNC-6 derivatives with domain deletions and mutants with selective unc-6 loss-of-function mutations were analyzed. The results indicate that the VI, V-2, and V-3 domains are primarily required for dorsal migrations and the VI and V-3 domains are required for ventral migrations. These domains are likely important for responses mediated by the UNC-5 and UNC-40 receptors, respectively. Deletion of V-3 and a V-3 point mutation selectively affect either cell or growth cone migrations, indicating that each migration requires unique interactions with UNC-6. Deletion of domain VI or of a conserved eight amino acid motif within VI causes loss of all UNC-6 guidance activities, and mutations within domain VI selectively affect different guidance activities, suggesting that domain VI regulates each response to UNC-6. We propose that individual UNC-6 domains mediate different signals, which act in parallel to regulate the morphological changes necessary for guidance.