title: The C domain of netrin UNC-6 silences calcium/calmodulin-dependent protein kinase- and diacylglycerol-dependent axon branching in Caenorhabditis elegans.
abstract: 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 Cbeta, 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-6DeltaC, 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-6DeltaC 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.
authors.affiliation: Department of Pathology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: William G
authors.initials: WG
authors.lastname: Wadsworth
mesh_terms: D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019852:Diacylglycerol Kinase / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D000075385:Netrins; D054799:Phospholipase C beta; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D004075:Diglycerides; D015801:Helminth Proteins; D007527:Isoenzymes; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075385:Netrins; D021122:Protein Subunits; D017476:Receptors, Neuropeptide Y; C078146:UNC-6 protein, C elegans; D019852:Diacylglycerol Kinase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517679:unc-43 protein, C elegans; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins