NH125 reduces the level of CPEB3, an RNA binding protein, to promote synaptic GluA2 expression

• Autores: Bender, Crhistian Luis; Yang, Qian; Sun, Lu; Liu, Siqiong June
• Año de publicación: 2016
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Ampa Receptors; Cerebellum; Cpeb3; Eef2; Eef2 Kinase; Glua2; Interneurons; Nh125; Protein Synthesis
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Neuronal activity can alter the phosphorylation state of eukaryotic elongation factor 2 (eEF2) and thereby regulates protein synthesis. This is thought to be the underlying mechanism for a form of synaptic plasticity that involves changes in the expression of synaptic AMPA type glutamate receptors. Phosphorylation of eEF2 by Ca/calmodulin-dependent eEF2 kinase reduces the activity of eEF2, and this is prevented by a commonly used eEF2 kinase inhibitor, NH125. Here we show that 10 μM NH125 increased the expression of synaptic GluA2-containing receptors in mouse cerebellar stellate cells and this was prevented by a protein synthesis inhibitor. However NH125 at 10 μM also reduced the level of CPEB3, a protein that is known to bind to GluA2 mRNA and suppress GluA2 (also known as GluR2) synthesis. In contrast, a low concentration of NH125 lowered the peEF2 level, but did not alter CPEB3 expression and also failed to increase synaptic GluA2 receptors. A selective eEF2 kinase inhibitor, A-484954, decreased the level of peEF2, without changing the expression of CPEB3. This suggests that reducing peEF2 does not lead to a decrease in CPEB3 levels and is not sufficient to increase GluA2 synthesis. Thus NH125 at 10 μM reduced the level of CPEB3, and promoted GluA2 translation via a mechanism independent of inhibition of eEF2 kinase. Therefore NH125 does not always alter protein synthesis via selective inhibition of eEF2 kinase and the effects of NH125 on translation of mRNAs should be interpreted with caution.
Fil: Bender, Crhistian Luis. Louisiana State University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Yang, Qian. Louisiana State University; Estados Unidos
Fil: Sun, Lu. Louisiana State University; Estados Unidos
Fil: Liu, Siqiong June. Louisiana State University; Estados Unidos