PT - JOURNAL ARTICLE AU - Qun Wang AU - William G. Wadsworth TI - The C Domain of Netrin UNC-6 Silences Calcium/Calmodulin-Dependent Protein Kinase- and Diacylglycerol-Dependent Axon Branching in <em>Caenorhabditis elegans</em> AID - 10.1523/JNEUROSCI.22-06-02274.2002 DP - 2002 Mar 15 TA - The Journal of Neuroscience PG - 2274--2282 VI - 22 IP - 6 4099 - http://www.jneurosci.org/content/22/6/2274.short 4100 - http://www.jneurosci.org/content/22/6/2274.full SO - J. Neurosci.2002 Mar 15; 22 AB - Second messenger systems mediate neuronal responses to extracellular factors that elicit axon branching, turning, and guidance. We found that mutations in Caenorhabditis elegans that affect components of second messenger systems, a G-protein subunit, phospholipase Cβ, diacylglycerol (DAG) kinase, and calcium/calmodulin-dependent protein kinase (CaMKII), have no obvious effect on axon responses to UNC-6 except in animals in which the N-terminal fragment, UNC-6ΔC, is expressed. In these animals, the mutations enhance or suppress ectopic branching of certain axons. Netrin UNC-6 is an extracellular protein that guides circumferential migrations, and UNC-6ΔC has UNC-6 guidance activity. We propose that the guidance response elicited by the UNC-6 N-terminal domains involves mechanisms that can induce branching that is sensitive to CaMKII- and DAG-dependent signaling, and that the UNC-6 C domain is required incis to the N-terminal domains to silence the branching and to maintain proper axon morphology.