Per citar aquest document: http://ddd.uab.cat/record/143276
Ras activation is a key event in activity-dependent survival of cerebellar granule neurons
Xifro Collsamata, Francesc Xavier (Universitat Autònoma de Barcelona. Institut de Neurociències)
Miñano Molina, Alfredo Jesús (Universitat Autònoma de Barcelona. Institut de Neurociències)
Saura Antolín, Carlos A. (Carlos Alberto) (Universitat Autònoma de Barcelona. Institut de Neurociències)
Rodríguez Álvarez, José (Universitat Autònoma de Barcelona. Institut de Neurociències)

Data: 2014
Resum: Neuronal activity promotes the survival of cerebellar granule neurons (CGNs) during the postnatal development of cerebellum. CGNs that fail to receive excitatory inputs will die by apoptosis. This process could be mimicked in culture by exposing CGNs to either a physiological concentration of KCl (5 mm or K5) plus N-methyl-d-aspartate (NMDA) or to 25 mm KCl (K25). We have previously described that a 24-h exposure to NMDA (100 μm) or K25 at 2 days in vitro induced long term survival of CGNs in K5 conditions. Here we have studied the molecular mechanisms activated at 2 days in vitro in these conditions. First we showed that NMDA or K25 addition promoted a rapid stimulation of PI3K and a biphasic phosphorylation on Ser-473 of Akt, a PI3K substrate. Interestingly, we demonstrated that only the first wave of Akt phosphorylation is necessary for the NMDA- and K25-mediated survival. Additionally, we detected that both NMDA and K25 increased ERK activity with a similar time-course. Moreover, our results showed that NMDA-mediated activation of the small G-protein Ras is necessary for PI3K/Akt pathway activation, whereas Rap1 was involved in NMDA phosphorylation of ERK. On the other hand, Ras, but not Rap1, mediates K25 activation of PI3K/Akt and MEK/ERK pathways. Because neuroprotection by NMDA or K25 is mediated by Ras (and not by Rap1) activation, we propose that Ras stimulation is a crucial event in NMDA- and K25-mediated survival of CGNs through the activation of PI3K/Akt and MEK/ERK pathways.
Nota: Número d'acord de subvenció MICINN/SAF2011-30281
Nota: Número d'acord de subvenció CIBERNED/CB06/05/0042
Nota: Número d'acord de subvenció AGAUR/SGR2009-1231
Drets: Tots els drets reservats.
Llengua: Anglès.
Document: article ; recerca ; publishedVersion
Matèria: Akt ; Apoptosis ; ERK ; Lentivirus ; Phosphatidylinositol 3-Kinase ; Rap-1 ; Potassium depolarization
Publicat a: The Journal of biological chemistry, Vol. 289, No. 12 (March 2014) , p. 8462–847, ISSN 0021-9258

DOI: 10.1074/jbc.M113.536375


12 p, 2.6 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Neurociències (INc)
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 Registre creat el 2015-11-17, darrera modificació el 2016-10-04



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