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2016-08

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/184407

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

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https://doi.org/10.1007/s12035-015-9335-7

Resum

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.

Matèries

Neurones, Proteïnes, Proteïna-tirosina-fosfatasa, Sinapsi

Matèries (anglès)

Neurons, Proteins, Protein-tyrosine phosphatase, Synapses

Citació

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Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

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. BDNF Induces Striatal-Enriched Protein Tyrosine Phosphatase 61 Degradation Through the Proteasome. _Molecular Neurobiology_. 2016. Vol. 53, núm. 6, pàgs. 4261-4273. [consulta: 25 de febrer de 2026]. ISSN: 0893-7648. [Disponible a: https://hdl.handle.net/2445/184407]

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