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, Panagiotis Z Anastasiadis, Erik M. Ullian, Louis F. Reichardt

Research output: Contribution to journalArticle

33 Citations (Scopus)

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

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Catenins
Protein-Tyrosine Kinases
Synapses
Synaptic Vesicles
Protein Phosphatase 2
Tics
Cell Adhesion
Tyrosine
Hippocampus

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

Lee, S. H., Peng, I. F., Ng, Y. G., Yanagisawa, M., Bamji, S. X., Elia, L. P., ... 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

Synapses are regulated by the cytoplasmic tyrosine kinase Fer in a pathway mediated by p120catenin, Fer, SHP-2, and β-catenin. / Lee, Seung Hye; Peng, I. Feng; Ng, Yu Gie; Yanagisawa, Masahiro; Bamji, Shernaz X.; Elia, Lisa P.; Balsamo, Janne; Lilien, Jack; Anastasiadis, Panagiotis Z; Ullian, Erik M.; Reichardt, Louis F.

In: Journal of Cell Biology, Vol. 183, No. 5, 01.12.2008, p. 893-908.

Research output: Contribution to journalArticle

Lee, SH, Peng, IF, Ng, YG, Yanagisawa, M, Bamji, SX, Elia, LP, Balsamo, J, Lilien, J, Anastasiadis, PZ, Ullian, EM & Reichardt, LF 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, vol. 183, no. 5, pp. 893-908. https://doi.org/10.1083/jcb.200807188
Lee, Seung Hye ; Peng, I. Feng ; Ng, Yu Gie ; Yanagisawa, Masahiro ; Bamji, Shernaz X. ; Elia, Lisa P. ; Balsamo, Janne ; Lilien, Jack ; Anastasiadis, Panagiotis Z ; Ullian, Erik M. ; Reichardt, Louis F. / Synapses are regulated by the cytoplasmic tyrosine kinase Fer in a pathway mediated by p120catenin, Fer, SHP-2, and β-catenin. In: Journal of Cell Biology. 2008 ; Vol. 183, No. 5. pp. 893-908.
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