The P2Y12 receptor regulates microglial activation by extracellular nucleotides
Top Cited Papers
- 19 November 2006
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 9 (12), 1512-1519
- https://doi.org/10.1038/nn1805
Abstract
Microglia are primary immune sentinels of the CNS. Following injury, these cells migrate or extend processes toward sites of tissue damage. CNS injury is accompanied by release of nucleotides, serving as signals for microglial activation or chemotaxis. Microglia express several purinoceptors, including a Gi-coupled subtype that has been implicated in ATP- and ADP-mediated migration in vitro. Here we show that microglia from mice lacking Gi-coupled P2Y12 receptors exhibit normal baseline motility but are unable to polarize, migrate or extend processes toward nucleotides in vitro or in vivo. Microglia in P2ry12−/− mice show significantly diminished directional branch extension toward sites of cortical damage in the living mouse. Moreover, P2Y12 expression is robust in the 'resting' state, but dramatically reduced after microglial activation. These results imply that P2Y12 is a primary site at which nucleotides act to induce microglial chemotaxis at early stages of the response to local CNS injury.This publication has 33 references indexed in Scilit:
- Early activation, motility, and homing of neonatal microglia to injured neurons does not require protein synthesisGlia, 2006
- BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic painNature, 2005
- Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in VivoScience, 2005
- P2Y1 and P2Y12 receptors for ADP desensitize by distinct kinase-dependent mechanismsBlood, 2005
- The glucocorticoid receptor blocks P-TEFb recruitment by NFκB to effect promoter-specific transcriptional repressionGenes & Development, 2005
- Selective expression of Gi/o‐coupled ATP receptor P2Y12 in microglia in rat brainGlia, 2003
- P2Y12, A New Platelet ADP Receptor, Target of ClopidogrelSeminars in Vascular Medicine, 2003
- ADP Is the Cognate Ligand for the Orphan G Protein-coupled Receptor SP1999Online Journal of Public Health Informatics, 2001
- A Role for Cdc42 in Macrophage ChemotaxisThe Journal of cell biology, 1998
- Microglia: a sensor for pathological events in the CNSTrends in Neurosciences, 1996