Synapses are regulated by the cytoplasmic tyrosine kinase Fer in a pathway mediated by p120catenin, Fer, SHP-2, and [beta]-catenin

• Published in: The Journal of cell biology Vol. 183; no. 5; p. 893
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Rockefeller University Press 01.12.2008
• Subjects: Cell adhesion & migration; Gene expression; Kinases; Signal transduction; Studies
• ISSN: 0021-9525; 1540-8140

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 β-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 β-catenin. β-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 b-catenin promotes excitatory synapse development and function. [PUBLICATION ABSTRACT]