The C domain of netrin UNC-6 silences calcium/calmodulin-dependent protein kinase- and diacylglycerol-dependent axon branching in Caenorhabditis elegans.
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.
Wang
Qun
Q
Department of Pathology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA.
Wadsworth
William G
WG
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
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