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P2y2 nucleotide receptor signaling is modulated by vitronectin receptors in human astrocytoma cells


, : P2y2 nucleotide receptor signaling is modulated by vitronectin receptors in human astrocytoma cells. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 515 1

Nucleotides released into the extracellular space from injured or dying neural cells can activate astrocytes via P2Y2 nucleotide receptors. It is recognized, that an RGD sequence in the first extracellular loop of the heptahelical P2Y2 nucleotide receptor interacts with vitronectin receptors and is required for effective signal transduction to focal adhesion kinase (FAK) and extracellular signal regulated kinases (ERK) 1/2. Our results demonstrate the importance of this interaction for P2Y2 mediated regulation of cell proliferation via the intracellular mitogen activated protein kinases (MAPK) cascade. Ligation of vitronectin receptors with specific antibodies caused an inhibition of P2Y2 receptor-induced extracellular signal regulated kinases (ERK1/2) and p38 phosphorylation. Coupling of P2Y2 receptor to ERK 1/2 was shown to induce cytoskeletal rearrangements causing membrane ruffles, which are an initial stage of cell motility. Stress fiber rearrangement was independent of P2Y2 receptor dependent p38 activation. Ligation of vitronectin receptors with specific antibodies partially inhibited P2Y2 receptor-induced membrane ruffling and DNA synthesis. These results suggest an important role for the interaction between P2Y2 nucleotide and vitronectin receptors in neural cells plasticity.

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