The autophagy-related kinase UNC-51 and its binding partner UNC-14 regulate the subcellular localization of the Netrin receptor UNC-5 inCaenorhabditis elegans
Open Access
- 1 September 2006
- journal article
- Published by The Company of Biologists in Development
- Vol. 133 (17), 3441-3450
- https://doi.org/10.1242/dev.02503
Abstract
UNC-51 and UNC-14 are required for the axon guidance of many neurons in Caenorhabditis elegans. UNC-51 is a serine/threonine kinase homologous to yeast Atg1, which is required for autophagy. The binding partner of UNC-51, UNC-14, contains a RUN domain that is predicted to play an important role in multiple Ras-like GTPase signaling pathways. How these molecules function in axon guidance is largely unknown. Here we observed that, in unc-51 and unc-14 mutants, UNC-5, the receptor for axon-guidance protein Netrin/UNC-6, abnormally localized in neuronal cell bodies. By contrast, the localization of many other proteins required for axon guidance was undisturbed. Moreover, UNC-5 localization was normal in animals with mutations in the genes for axon guidance proteins, several motor proteins, vesicle components and autophagy-related proteins. We also found that unc-5 and unc-6 interacted genetically with unc-51 and unc-14 to affect axon guidance, and that UNC-5 co-localized with UNC-51 and UNC-14 in neurons. These results suggest that UNC-51 and UNC-14 regulate the subcellular localization of the Netrin receptor UNC-5, and that UNC-5 uses a unique mechanism for its localization; the functionality of UNC-5 is probably regulated by this localization.Keywords
This publication has 51 references indexed in Scilit:
- Regulatory machinery of UNC‐33 Ce‐CRMP localization in neurites during neuronal development in Caenorhabditis elegansJournal of Neurochemistry, 2005
- Molecular Mechanisms of Axon GuidanceScience, 2002
- MAX-1, a Novel PH/MyTH4/FERM Domain Cytoplasmic Protein Implicated in Netrin-Mediated Axon RepulsionNeuron, 2002
- On the Role of RNA Amplification in dsRNA-Triggered Gene SilencingCell, 2001
- RUN domains: a new family of domains involved in Ras-like GTPase signalingTrends in Biochemical Sciences, 2001
- The UNC-14 protein required for axonal elongation and guidance in Caenorhabditis elegans interacts with the serine/threonine kinase UNC-51.Genes & Development, 1997
- Caenorhabditis elegans unc-51 gene required for axonal elongation encodes a novel serine/threonine kinase.Genes & Development, 1994
- The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6Cell, 1994
- Cloning by insertional mutagenesis of a cDNA encoding Caenorhabditis elegans kinesin heavy chain.Proceedings of the National Academy of Sciences of the United States of America, 1993
- The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegansNeuron, 1990