The short coiled-coil domain-containing protein UNC-69 cooperates with UNC-76 to regulate axonal outgrowth and normal presynaptic organization in Caenorhabditis elegans
| Autor: | Su, C W, Tharin, S, Jin, Y, Wightman, B, Spector, M, Meili, D, Tsung, N, Rhiner, C, Bourikas, D, Stoeckli, E T, Garriga, G, Horvitz, H R, Hengartner, M O |
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| Přispěvatelé: | University of Zurich, Hengartner, M O, Massachusetts Institute of Technology. Department of Biology, Horvitz, H. Robert, Tsung, Nancy |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
fungi
Neuropeptides Kinesins Biological Transport macromolecular substances 1100 General Agricultural and Biological Sciences Axons 10124 Institute of Molecular Life Sciences lcsh:Biology (General) nervous system 1300 General Biochemistry Genetics and Molecular Biology Synapses Animals 570 Life sciences biology Caenorhabditis elegans Proteins lcsh:QH301-705.5 Research Article |
| Zdroj: | Journal of Biology BioMed Central Ltd Journal of Biology, Vol 5, Iss 4, p 9 (2006) |
| Popis: | Background: The nematode Caenorhabditis elegans has been used extensively to identify the genetic requirements for proper nervous system development and function. Key to this process is the direction of vesicles to the growing axons and dendrites, which is required for growth-cone extension and synapse formation in the developing neurons. The contribution and mechanism of membrane traffic in neuronal development are not fully understood, however. Results: We show that the C. elegans gene unc-69 is required for axon outgrowth, guidance, fasciculation and normal presynaptic organization. We identify UNC-69 as an evolutionarily conserved 108-amino-acid protein with a short coiled-coil domain. UNC-69 interacts physically with UNC-76, mutations in which produce similar defects to loss of unc-69 function. In addition, a weak reduction-of-function allele, unc-69(ju69), preferentially causes mislocalization of the synaptic vesicle marker synaptobrevin. UNC-69 and UNC-76 colocalize as puncta in neuronal processes and cooperate to regulate axon extension and synapse formation. The chicken UNC-69 homolog is highly expressed in the developing central nervous system, and its inactivation by RNA interference leads to axon guidance defects. Conclusion: We have identified a novel protein complex, composed of UNC-69 and UNC-76, which promotes axonal growth and normal presynaptic organization in C. elegans. As both proteins are conserved through evolution, we suggest that the mammalian homologs of UNC-69 and UNC-76 (SCOCO and FEZ, respectively) may function similarly. Rita Allen Foundation March of Dimes Birth Defects Foundation Ernst Hadorn Foundation Swiss National Science Foundation National Institutes of Health (U.S.) (Grant GM24663) Howard Hughes Medical Institute |
| Databáze: | OpenAIRE |
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