"PROTEIN TYROSINE PHOSPHATASE PTP1B IS REQUIRED FOR SYNAPSE FORMATION".

FEDERICO FUENTES; ZIMMER D; DEJONGHE B; BENCE K; C. O. ARREGUI

Huerta Grande - Córdoba

Congreso; XXVI Annual Meeting of the Argentine Society for Neurochemistry (SAN).; 2011

Sociedad Argentina de Investigación en Neurociencias (SAN)

Protein tyrosine phosphatase PTP1B dephosphorylates B-catenin and promotesits binding to the N-cadherin cytoplasmic domain. We have recently shown thatPTP1B localizes in dendrites, suggesting a role in the synaptic compartment.Here we show, by double fluorescence time-lapse analysis, that GFP-PTP1Binvades transiently dendritic spines of hippocampal neurons in culture. GFPPTP1Boverexpression does not affect filopodial density and length. Dominantnegative disruption of PTP1B function and gene deletion, lead to increased lengthof dendritic filopodia and reduction of mushroom-like spines, accompanied by adisorganization of pre- and post-synapsis, as judged by decreased clustering ofsynapsin-1 and PSD-95. Immunoprecipitation of N-cadherin from hippocampi ofadult wild type (WT) and PTP1B knockout (KO) mice reveals a 30% reduction inthe amount of associated B-catenin in KO mice. This is accompanied by a ~5-fold increase in the levels of phosphorylated tyrosine 654 on B-catenin. BDNFdependentphosphorylation of B-catenin Tyr-654 is attenuated by PTP1B. Ourresults suggest that PTP1B is required for synapse maturation, likely by modulatingN-cadherin-mediated adhesion through B-catenin dephosphorylation of Tyr-654.