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The Journal of Neuroscience, March 15, 2002, 22(6):2274-2282

The C Domain of Netrin UNC-6 Silences Calcium/Calmodulin-Dependent Protein Kinase- and Diacylglycerol-Dependent Axon Branching in Caenorhabditis elegans

Qun Wang and William G. Wadsworth

Department of Pathology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635

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 C, 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-6C, 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-6C 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 in cis to the N-terminal domains to silence the branching and to maintain proper axon morphology.

Key words: netrin; UNC-6; Caenorhabditis elegans; guidance; axon branching; genetics; G-protein subunit; Gq; phospholipase C; PLC; diacylglycerol kinase; DAK; calcium/calmodulin-dependent protein kinase; CaMKII; neuropeptide Y receptor

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Copyright © 2002 Society for Neuroscience  0270-6474/02/2262274-09$05.00/0

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				R. P. Kruger, J. Lee, W. Li, and K.-L. Guan Mapping Netrin Receptor Binding Reveals Domains of Unc5 Regulating Its Tyrosine Phosphorylation J. Neurosci., December 1, 2004; 24(48): 10826 - 10834. [Abstract] [Full Text] [PDF]

				Y.-s. Lim and W. G. Wadsworth Identification of Domains of Netrin UNC-6 that Mediate Attractive and Repulsive Guidance and Responses from Cells and Growth Cones J. Neurosci., August 15, 2002; 22(16): 7080 - 7087. [Abstract] [Full Text] [PDF]

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