Saavedra, AnaPuigdellívol Cañadell, Maria del MarTyebji, ShirazKurup, PradeepXu, JianGinés Padrós, SilviaAlberch i Vié, Jordi, 1959-Lombroso, Paul J.Pérez Navarro, Esther2022-03-252022-03-252016-080893-7648https://hdl.handle.net/2445/184407Brain-derived neurotrophic factor (BDNF) promotes synaptic strengthening through the regulation of kinase and phosphatase activity. Conversely, striatal-enriched protein tyrosine phosphatase (STEP) opposes synaptic strengthening through inactivation or internalization of signaling molecules. Here, we investigated whether BDNF regulates STEP levels/activity. BDNF induced a reduction of STEP61 levels in primary cortical neurons, an effect that was prevented by inhibition of tyrosine kinases, phospholipase C gamma, or the ubiquitin-proteasome system (UPS). The levels of pGluN2B(Tyr1472) and pERK1/2(Thr202/Tyr204), two STEP substrates, increased in BDNF-treated cultures, and blockade of the UPS prevented STEP61 degradation and reduced BDNF-induced GluN2B and ERK1/2 phosphorylation. Moreover, brief or sustained cell depolarization reduced STEP61 levels in cortical neurons by different mechanisms. BDNF also promoted UPS-mediated STEP61 degradation in cultured striatal and hippocampal neurons. In contrast, nerve growth factor and neurotrophin-3 had no effect on STEP61 levels. Our results thus indicate that STEP61 degradation is an important event in BDNF-mediated effects.13 p.application/pdfeng(c) Humana Press., 2016NeuronesProteïnesProteïna-tirosina-fosfatasaSinapsiNeuronsProteinsProtein-tyrosine phosphataseSynapsesinfo:eu-repo/semantics/article6546202022-03-25info:eu-repo/semantics/openAccess26223799