PT  - JOURNAL ARTICLE
AU  - Lim, Yoo-shick
AU  - Wadsworth, William G.
TI  - Identification of Domains of Netrin UNC-6 that Mediate Attractive and Repulsive Guidance and Responses from Cells and Growth Cones
AID  - 10.1523/JNEUROSCI.22-16-07080.2002
DP  - 2002 Aug 15
TA  - The Journal of Neuroscience
PG  - 7080--7087
VI  - 22
IP  - 16
4099  - http://www.jneurosci.org/content/22/16/7080.short
4100  - http://www.jneurosci.org/content/22/16/7080.full
SO  - J. Neurosci.2002 Aug 15; 22
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.