Investigate the NMDAR-dependent β-catenin synaptic translocation via tyrosine phosphorylation

• Main Authors: Szu-Chi Ho, 何思祈
• Other Authors: Chin-Yin Tai
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/37674491669316626732

碩士 === 國立陽明大學 === 生命科學暨基因體科學研究所 === 99 === Synapse is a junction that mediating neural transmission between two neurons. N-cadherin is a cell adhesion molecule at synapses. It mediates actin cytoskeleton organization and transsynaptic communication through the interaction with β-catenin and α-catenin. Beta-catenin responds to NMDAR activation and stabilizes N-cadherin at the surface. Previous studies have suggested that NMDAR-dependent neural activity drives β-catenin accumulated in spines possibly through the dephosphorylation of multiple tyrosine residues. Beta-catenin Y654 residue has been found to be one of these sites, however, a few other sites remain to be investigated. Here, we found that phosphorylation on β-catenin Y142 residue was reduced upon NMDA treatment. By infecting neurons with GFP fusioned β-catenin Y142F, a phosphorylation-prevented mutant, we observed that NMDA-dependent β-catenin spine accumulation was not inhibited by this construct. However, no accumulation of this mutant in the spine was observed in genistein-treated neurons comparing to theβ-catenin WT control group. This result suggests that regulation of phosphorylation on β-catenin Y142 residue is important for β-catenin spine accumulation. Since β-catenin is known as a coactivator in neuceli, we also examined the subcellular localization of β-catenin by immunostaining to observe whether NMDA can drive β-catenin not only into the spines but also into the nuclei. No endogenous β-catenin was observed in the nuclei upon NMDA treatment, suggesting that NMDA-dependent β-catenin synaptic translocation was not result from activation of its target genes.