The P2Y12 receptor regulates microglial activation by extracellular nucleotides

Sharon E Haynes; Gunther Hollopeter; Guang Yang; Dana Kurpius; Michael E Dailey; Wen-Biao Gan; David Julius

doi:10.1038/nn1805

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The P2Y12 receptor regulates microglial activation by extracellular nucleotides

Journal article

Peer reviewed

The P2Y12 receptor regulates microglial activation by extracellular nucleotides

Sharon E Haynes, Gunther Hollopeter, Guang Yang, Dana Kurpius, Michael E Dailey, Wen-Biao Gan and David Julius

Nature neuroscience, Vol.9(12), pp.1512-1519

12/2006

DOI: 10.1038/nn1805

PMID: 17115040

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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 G(i)-coupled subtype that has been implicated in ATP- and ADP-mediated migration in vitro. Here we show that microglia from mice lacking G(i)-coupled P2Y(12) receptors exhibit normal baseline motility but are unable to polarize, migrate or extend processes toward nucleotides in vitro or in vivo. Microglia in P2ry(12)(-/-) mice show significantly diminished directional branch extension toward sites of cortical damage in the living mouse. Moreover, P2Y(12) expression is robust in the 'resting' state, but dramatically reduced after microglial activation. These results imply that P2Y(12) is a primary site at which nucleotides act to induce microglial chemotaxis at early stages of the response to local CNS injury.

Microglia - metabolism

Adenosine Triphosphate - secretion

Membrane Proteins - immunology

Brain Injuries - metabolism

Adenosine Diphosphate - physiology

Central Nervous System - immunology

Mice, Knockout

Animals

Chemotaxis - physiology

Microglia - immunology

Brain Injuries - immunology

Central Nervous System - cytology

Receptors, Purinergic P2 - metabolism

Receptors, Purinergic P2Y12

Adenosine Diphosphate - secretion

Membrane Proteins - metabolism

Mice

Adenosine Triphosphate - physiology

Receptors, Purinergic P2 - immunology

Details

Title: Subtitle: The P2Y12 receptor regulates microglial activation by extracellular nucleotides
Creators: Sharon E Haynes - Department of Physiology & Cellular, University of California, San Francisco (UCSF), 600 16th Street, San Francisco, California 94158-2517, USA
Gunther Hollopeter
Guang Yang
Dana Kurpius
Michael E Dailey
Wen-Biao Gan
David Julius
Resource Type: Journal article
Publication Details: Nature neuroscience, Vol.9(12), pp.1512-1519
Publisher: United States
DOI: 10.1038/nn1805
PMID: 17115040
ISSN: 1097-6256
eISSN: 1546-1726
Grant note: S10 RR017941 / NCRR NIH HHS R01 NS043468 / NINDS NIH HHS NS434468 / NINDS NIH HHS
Language: English
Date published: 12/2006
Academic Unit: Iowa Neuroscience Institute; Biology
Record Identifier: 9984070369102771

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