Journal article
Expression of [CX.sub.3]CR1 chemokine receptors on neurons and their role in neuronal survival
Proceedings of the National Academy of Sciences - PNAS, Vol.97(14), p8075
05 Jul 2000
Abstract
Recent in vitro and in vivo studies have shown that the chemokine fractalkine is widely expressed in the brain and localized principally to neurons. Central nervous system expression of [CX.sub.3]CR1, the only known receptor for fractalkine, has been demonstrated exclusively on microglia and astrocytes. Thus, it has been proposed that fractalkine regulates cellular communication between neurons (that produce fractalkine) and microglia (that express its receptor). Here we show, for the first time, that hippocampal neurons also express [CX.sub.3]CR1. Receptor activation by soluble fractalkine induces activation of the protein kinase Akt, a major component of prosurvival signaling pathways, and nuclear translocation of NF-[Kappa]B, a downstream effector of Akt. Fractalkine protects hippocampal neurons from the neurotoxicity induced by the HIV-1 envelope protein [gp120.sub.IIIB], an effect blocked by anti-[CX.sub.3]CR1 antibodies. Experiments with two different inhibitors of the phosphatidylinositol 3-kinase, a key enzyme in the activation of Akt, and with a phospholipid activator of Akt demonstrate that Akt activation is responsible for the neuroprotective effects of fractalkine. These data show that neuronal [CX.sub.3]CR1 receptors mediate the neurotrophic effects of fractalkine, suggesting that fractalkine and its receptor are involved in a complex network of both paracrine and autocrine interactions between neurons and glia.
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Details
- Title
- Expression of [CX.sub.3]CR1 chemokine receptors on neurons and their role in neuronal survival
- Creators
- Olimpia MeucciAlessandro FatatisArthur A SimenRichard J Miller
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.97(14), p8075
- Publisher
- National Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Identifiers
- 991020111091104721