Synapses are regulated by the cytoplasmic tyrosine kinase Fer in a pathway mediated by p120catenin, Fer, SHP-2, and beta-catenin
| Autor: | Lee, Seung-Hye, Peng, I-Feng, Ng, Yu Gie, Yanagisawa, Masahiro, Bamji, Shernaz X, Elia, Lisa P, Balsamo, Janne, Lilien, Jack, Anastasiadis, Panos Z, Ullian, Erik M, Reichardt, Louis F |
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| Rok vydání: | 2008 |
| Předmět: |
Cytoplasm
animal structures Time Factors Cells Presynaptic Terminals Small Interfering Transfection Hippocampus Synaptic Transmission Non-Receptor Type 11 Medical and Health Sciences Animals Phosphorylation beta Catenin Neurons Cultured Excitatory Postsynaptic Potentials Catenins Protein-Tyrosine Kinases Biological Sciences Phosphoproteins Axons Rats RNA RNA Interference Sprague-Dawley Protein Tyrosine Phosphatase rhoA GTP-Binding Protein Cell Adhesion Molecules Developmental Biology |
| Zdroj: | The Journal of cell biology, vol 183, iss 5 |
| Popis: | Localization of presynaptic components to synaptic sites is critical for hippocampal synapse formation. Cell adhesion-regulated signaling is important for synaptic development and function, but little is known about differentiation of the presynaptic compartment. In this study, we describe a pathway that promotes presynaptic development involving p120catenin (p120ctn), the cytoplasmic tyrosine kinase Fer, the protein phosphatase SHP-2, and beta-catenin. Presynaptic Fer depletion prevents localization of active zone constituents and synaptic vesicles and inhibits excitatory synapse formation and synaptic transmission. Depletion of p120ctn or SHP-2 similarly disrupts synaptic vesicle localization with active SHP-2, restoring synapse formation in the absence of Fer. Fer or SHP-2 depletion results in elevated tyrosine phosphorylation of beta-catenin. beta-Catenin overexpression restores normal synaptic vesicle localization in the absence of Fer or SHP-2. Our results indicate that a presynaptic signaling pathway through p120ctn, Fer, SHP-2, and beta-catenin promotes excitatory synapse development and function. |
| Databáze: | OpenAIRE |
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