• Molecular neurobiology · Aug 2016

    BDNF Induces Striatal-Enriched Protein Tyrosine Phosphatase 61 Degradation Through the Proteasome.

    • Ana Saavedra, Mar Puigdellívol, Shiraz Tyebji, Pradeep Kurup, Jian Xu, Silvia Ginés, Jordi Alberch, Paul J Lombroso, and Esther Pérez-Navarro.
    • Departament de Biologia Cel · lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Casanova 143, 08036, Barcelona, Catalonia, Spain.
    • Mol. Neurobiol. 2016 Aug 1; 53 (6): 4261-4273.

    AbstractBrain-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.

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