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http://hdl.handle.net/2445/184407
Title: | BDNF Induces Striatal-Enriched Protein Tyrosine Phosphatase 61 Degradation Through the Proteasome |
Author: | Saavedra, Ana Puigdellívol Cañadell, Maria del Mar Tyebji, Shiraz Kurup, Pradeep Xu, Jian Ginés Padrós, Silvia Alberch i Vié, Jordi Lombroso, Paul J. Pérez Navarro, Esther |
Keywords: | Neurones Proteïnes Proteïna-tirosina-fosfatasa Sinapsi Neurons Proteins Protein-tyrosine phosphatase Synapses |
Issue Date: | Aug-2016 |
Publisher: | Humana Press. |
Abstract: | Brain-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. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1007/s12035-015-9335-7 |
It is part of: | Molecular Neurobiology, 2016, vol. 53, num. 6, p. 4261-4273 |
URI: | http://hdl.handle.net/2445/184407 |
Related resource: | https://doi.org/10.1007/s12035-015-9335-7 |
ISSN: | 0893-7648 |
Appears in Collections: | Articles publicats en revistes (Biomedicina) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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