Reference - Detail
|Author||Ogura K, Okada T, Mitani S, Gengyo-Ando K, Baillie DL, Kohara Y, Goshima Y.|
|Title||Protein phosphatase 2A cooperates with the autophagy-related kinase UNC-51 to regulate axon guidance in Caenorhabditis elegans.|
UNC-51 is a serine/threonine protein kinase conserved from yeast to humans. The yeast homolog Atg1 regulates autophagy (catabolic membrane trafficking) required for surviving starvation. In C. elegans, UNC-51 regulates the axon guidance of many neurons by a different mechanism than it and its homologs use for autophagy. UNC-51 regulates the subcellular localization (trafficking) of UNC-5, a receptor for the axon guidance molecule UNC-6/Netrin; however, the molecular details of the role for UNC-51 are largely unknown. Here, we report that UNC-51 physically interacts with LET-92, the catalytic subunit of serine/threonine protein phosphatase 2A (PP2A-C), which plays important roles in many cellular functions. A low allelic dose of LET-92 partially suppressed axon guidance defects of weak, but not severe, unc-51 mutants, and a low allelic dose of PP2A regulatory subunits A (PAA-1/PP2A-A) and B (SUR-6/PP2A-B) partially enhanced the weak unc-51 mutants. We also found that LET-92 can work cell-non-autonomously on axon guidance in neurons, and that LET-92 colocalized with UNC-51 in neurons. In addition, PP2A dephosphorylated phosphoproteins that had been phosphorylated by UNC-51. These results suggest that, by forming a complex, PP2A cooperates with UNC-51 to regulate axon guidance by regulating phosphorylation. This is the first report of a serine/threonine protein phosphatase functioning in axon guidance in vivo.
|MeSH||Amino Acid Sequence Animals Animals, Genetically Modified Autophagy / genetics Autophagy / physiology Axonal Transport / genetics Axonal Transport / physiology Axons / metabolism Axons / physiology* Caenorhabditis elegans / genetics* Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* Molecular Sequence Data Neurogenesis / genetics Neurogenesis / physiology Phosphorylation / genetics Protein Binding / physiology Protein Kinases / metabolism Protein Kinases / physiology Protein Phosphatase 2 / genetics Protein Phosphatase 2 / metabolism Protein Phosphatase 2 / physiology* Protein Subunits / genetics Protein Subunits / metabolism Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism Protein-Serine-Threonine Kinases / physiology* Sequence Homology, Amino Acid Synaptic Transmission / genetics Synaptic Transmission / physiology|
|WOS Category||DEVELOPMENTAL BIOLOGY|