Anales RANF

P.53 P2X7 RECEPTOR REGULATES THE INDUCIBLE NUCLEAR DUAL-SPECIFICITY PHOSPHATASE 1 IN RAT CEREBELLAR ASTROCYTES J.C. Gil-Redondo, M.J. Queipo, L. Paniagua-Herranz, R. Pérez-Sen, M.T. Miras Portugal, E.G. Delicado Complutense University of Madrid, Madrid, Spain P2X7 is an ATP-gated ion channel belonging to the P2X receptor family. P2X7 receptors can activate several signaling pathways, including MAP kinase cascades. Mitogen Activated Protein Kinases comprise several serine-threonine kinases that mediate proliferation, differentiation and cell survival/death. Since these MAP kinases regulate important processes in the cell, it is necessary to know the signaling responsible for their dephosphorylation and deactivation. Several groups of phosphatases participate in this deactivation, being the MAP kinase phosphatases (MKPs) the main group. MKPs are Dual Specificity Phosphatases (DUSPs), which dephosphorylate both serine/threonine and tyrosine residues in the same substrate. There are different groups of MKPs, depending on the intracellular location of the phosphatase and the affinity for each MAP kinase. MKPs activity is regulated at different levels, translational and posttranslational modifications, by their MAPK substrates [1]. In addition, the MAPK itself is able to induce transcription of the genes encoding the phosphatases. In previous work, we showed that P2X7 receptors modulate the levels of the cytosolic ERK-selective protein phosphatase DUSP6 with a biphasic pattern and in an ERK-dependent manner in rat cerebellar astrocytes [2]. In the present work, we focus on the characterization of the intracellular mechanisms responsible for the regulation of the nuclear inducible phosphatase MKP-1/DUSP1 by P2X7 receptors. In contrast to that reported for DUSP6, the regulation of DUSP1 expression is dependent on ERK and p38 activation. DUSP1 appears to be involved in the dephosphorylation of p38 at the nuclear compartment. [1] Caunt CJ, Keyse SM (2013) Dual-specificity MAP kinase phosphatases (MKPs): shaping the outcome of MAP kinase signalling. FEBS J 280:489-504. [2] Queipo, MJ, Gil-Redondo, JC, et al. (2018) P2X7 Nucleotide and EGF receptors exert dual modulation of the Dual-specificity Phosphatase 6 (MKP-3) in granule neurons and astrocytes, contributing to negative feedback on ERK signaling. Front Mol Neurosci 10.