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

Seung Hye Lee, I. Feng Peng, Yu Gie Ng, Masahiro Yanagisawa, Shernaz X. Bamji, Lisa P. Elia, Janne Balsamo, Jack Lilien, Panos Z. Anastasiadis, Erik M. Ullian, Louis F. Reichardt

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

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 synap-tic 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 phosphoryla-tion of βcatenin. βCatenin 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 βcatenin promotes excitatory synapse development and function.

Original languageEnglish (US)
Pages (from-to)893-908
Number of pages16
JournalJournal of Cell Biology
Volume183
Issue number5
DOIs
StatePublished - Dec 1 2008

ASJC Scopus subject areas

  • Cell Biology

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    Lee, S. H., Peng, I. F., Ng, Y. G., Yanagisawa, M., Bamji, S. X., Elia, L. P., Balsamo, J., Lilien, J., Anastasiadis, P. Z., Ullian, E. M., & Reichardt, L. F. (2008). Synapses are regulated by the cytoplasmic tyrosine kinase Fer in a pathway mediated by p120catenin, Fer, SHP-2, and β-catenin. Journal of Cell Biology, 183(5), 893-908. https://doi.org/10.1083/jcb.200807188