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pubmed:abstractText |
Cell survival is an essential function in the development and maintenance of the nervous system. We demonstrate here a previously unappreciated role for extracellular nucleotide signaling through the P2Y2 receptor in the survival of neurons: PC12 (pheochromocytoma 12) cells and dorsal root ganglion neurons are protected from serum starvation-induced apoptosis by ATP, UTP, and ATPgammaS, an effect mediated via P2Y2 receptors, as demonstrated by small interfering RNA and genetic knock-out models. This protection occurs independently of neurophin signaling but requires Src activation of ERK (extracellular signal-regulated kinase) and Akt. Moreover, ATPgammaS and NGF act synergistically to enhance neuronal survival through enhanced TrkA signaling. The results, which define a novel mechanism for inhibition of apoptosis, implicate parallel, interacting systems--extracellular nucleotides/P2Y2 receptors and neurotrophin/TrkA--to sustain neuronal survival.
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pubmed:affiliation |
Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA.
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