The P2Y12 receptor regulates microglial activation by extracellular nucleotides

Related Experiment Video

Updated: Jul 18, 2026

Real-time Live-cell Flow Cytometry to Investigate Calcium Influx, Pore Formation, and Phagocytosis by P2X7 Receptors in Adult Neural Progenitor Cells
11:47

Real-time Live-cell Flow Cytometry to Investigate Calcium Influx, Pore Formation, and Phagocytosis by P2X7 Receptors in Adult Neural Progenitor Cells

Published on: April 3, 2019

Sharon E Haynes1, Gunther Hollopeter, Guang Yang

  • 1Department of Physiology & Cellular, University of California, San Francisco (UCSF), 600 16th Street, San Francisco, California 94158-2517, USA.

Nature Neuroscience
|November 23, 2006
PubMed

Insights

The P2Y12 receptor is crucial for microglia, the brain's immune cells, to move towards injury sites. Without it, microglia cannot effectively respond to chemical signals after central nervous system damage.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are key immune cells in the central nervous system (CNS).
  • CNS injury triggers nucleotide release, signaling microglial activation and migration.
  • Microglia possess purinoceptors, including a G(i)-coupled subtype involved in migration.

Purpose of the Study:

  • To investigate the role of the G(i)-coupled P2Y12 receptor in microglial chemotaxis and response to CNS injury.
  • To determine if P2Y12 is essential for microglial polarization, migration, and process extension towards nucleotides.

Main Methods:

  • Utilized P2Y12 receptor-deficient mice (P2ry(12)(-/-)).
  • Assessed microglial motility, polarization, and process extension in vitro and in vivo.
  • Examined microglial response to nucleotides and cortical damage in living mice.

Main Results:

  • Microglia lacking P2Y12 receptors showed normal baseline motility but failed to polarize or migrate towards nucleotides.
  • P2ry(12)(-/-) mice exhibited significantly reduced directional microglial branch extension towards cortical damage.
  • P2Y12 receptor expression was high in resting microglia but decreased upon activation.

Conclusions:

  • The P2Y12 receptor is essential for nucleotide-induced microglial chemotaxis in response to CNS injury.
  • P2Y12 mediates directional migration and process extension of microglia towards sites of damage.
  • P2Y12 acts as a critical sensor for early microglial responses to local CNS injury.

More Related Videos

Primary Microglia Isolation from Mixed Glial Cell Cultures of Neonatal Rat Brain Tissue10:20

Primary Microglia Isolation from Mixed Glial Cell Cultures of Neonatal Rat Brain Tissue

Published on: August 15, 2012

Related Concept Videos

GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors01:20

Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors

Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...