The conserved kinase UNC-51 acts with VAB-8 and UNC-14 to regulate axon outgrowth in C. elegans.
Directional cues guide growth cones. While molecules like UNC-6/netrin direct migrations along the dorsoventral axis of many organisms, it is unclear how anteroposterior guidance is achieved. We describe a physical interaction between VAB-8, a protein both necessary and sufficient for posteriorly directed migrations in C. elegans, and UNC-51, a conserved serine/threonine kinase that functions generally in axon outgrowth. We show that both proteins function in the CAN neurons to direct their axons posteriorly. Expression in the CANs of peptides predicted to interfere with interactions between UNC-51 and both VAB-8 and UNC-14, a second protein that interacts physically with UNC-51, disrupts CAN axon outgrowth. We provide genetic evidence that VAB-8 functions in an UNC-51 pathway for posteriorly directed CAN axon guidance and show that VAB-8 and UNC-14 can be targets of UNC-51 kinase activity. Taken together, our results suggest that VAB-8 and UNC-14 are substrates that mediate the function of UNC-51 in axon outgrowth.
Lai
Tina
T
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Garriga
Gian
G
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D014162:Transfection; D020798:Two-Hybrid System Techniques
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D010455:Peptides; C107406:UNC-14 protein, C elegans; C112201:vab-8 protein, C elegans; C112443:UNC-51 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D010744:Phosphoric Monoester Hydrolases