P2Y4 receptor-mediated pinocytosis contributes to amyloid beta-induced self-uptake by microglia.

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.

journal_name

Mol Cell Biol

authors

Li HQ,Chen C,Dou Y,Wu HJ,Liu YJ,Lou HF,Zhang JM,Li XM,Wang H,Duan S

doi

10.1128/MCB.00544-13

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

4282-93

issue

21

eissn

0270-7306

issn

1098-5549

pii

MCB.00544-13

journal_volume

33

pub_type

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