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Updated: May 8, 2026
Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia
Published on: November 9, 2018
P2Y4 receptor-mediated pinocytosis contributes to amyloid beta-induced self-uptake by microglia
Hui-quan Li1, Cong Chen, Ying Dou
1Institute of Neuroscience and Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Abstract:
Brain disturbances, like injuries or aberrant protein deposits, evoke nucleotide release or leakage from cells, leading to microglial chemotaxis and ingestion. Recent studies have identified P2Y12 purinergic receptors as triggers for microglial chemotaxis and P2Y6 receptors as mediators for phagocytosis. However, pinocytosis, known as the internalization of fluid-phase materials, has received much less attention. We found that ATP efficiently triggered pinocytosis in microglia. Pharmacological analysis and knockdown experiments demonstrated the involvement of P2Y4 receptors and the phosphatidylinositol 3-kinase/Akt cascade in the nucleotide-induced pinocytosis. Further evidence indicated that soluble amyloid beta peptide 1-42 induced self-uptake in microglia through pinocytosis, a process involving activation of P2Y4 receptors by autocrine ATP signaling. Our results demonstrate a previously unknown function of ATP as a "drink me" signal for microglia and P2Y4 receptors as a potential therapeutic target for the treatment of Alzheimer's disease.
Insights
Adenosine triphosphate (ATP) acts as a "drink me" signal, activating pinocytosis in microglia via P2Y4 receptors. This finding reveals P2Y4 receptors as a potential therapeutic target for Alzheimer's disease.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Microglia, the brain's immune cells, respond to injury by releasing nucleotides.
- P2Y12 and P2Y6 receptors mediate microglial chemotaxis and phagocytosis, respectively.
- Pinocytosis in microglia remains less understood.
Purpose of the Study:
- To investigate the role of adenosine triphosphate (ATP) in microglial pinocytosis.
- To identify the specific purinergic receptors and signaling pathways involved in nucleotide-induced pinocytosis.
- To explore the therapeutic potential of targeting these pathways in Alzheimer's disease.
Main Methods:
- Utilized pharmacological analysis and knockdown experiments in microglia.
- Investigated ATP-induced pinocytosis.
- Examined the role of P2Y4 receptors and the phosphatidylinositol 3-kinase/Akt cascade.
- Assessed the uptake of amyloid beta peptide 1-42 by microglia.
Main Results:
- Adenosine triphosphate (ATP) was found to efficiently trigger pinocytosis in microglia.
- P2Y4 receptors and the phosphatidylinositol 3-kinase/Akt signaling pathway were identified as key mediators.
- Soluble amyloid beta peptide 1-42 induced microglial self-uptake via pinocytosis, involving P2Y4 receptor activation by autocrine ATP signaling.
Conclusions:
- ATP functions as a novel "drink me" signal for microglia, initiating pinocytosis.
- P2Y4 receptors are crucial for nucleotide-induced pinocytosis and amyloid beta uptake.
- Targeting P2Y4 receptors presents a potential therapeutic strategy for Alzheimer's disease.
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