Journal article
Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival
Proceedings of the National Academy of Sciences - PNAS, v 97(14), pp 8075-8080
05 Jul 2000
PMID: 10869418
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 CX3CR1, 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 CX3CR1. Receptor activation by soluble fractalkine induces activation of the protein kinase Akt, a major component of prosurvival signaling pathways, and nuclear translocation of NF-κB, a downstream effector of Akt. Fractalkine protects hippocampal neurons from the neurotoxicity induced by the HIV-1 envelope protein gp120IIIB, an effect blocked by anti-CX3CR1 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 CX3CR1 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 CX3CR1 chemokine receptors on neurons and their role in neuronal survival
- Creators
- Olimpia Meucci - Drexel University, Pharmacology and PhysiologyAlessandro Fatatis - Drexel University, Pharmacology and PhysiologyArthur A. Simen - Department of Neurobiology, Pharmacology, and Physiology, and Committee on Neurobiology, University of Chicago, Chicago, IL 60637Richard J. Miller - Department of Neurobiology, Pharmacology, and Physiology, and Committee on Neurobiology, University of Chicago, Chicago, IL 60637
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 97(14), pp 8075-8080
- Publisher
- The National Academy of Sciences
- Number of pages
- 6
- Grant note
- NICHD NIH HHS: T32 HD007009 NIDA NIH HHS: DA02121 NINDS NIH HHS: P01 NS021442, NS33826 PHS HHS: MC40165
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000088048400075
- Scopus ID
- 2-s2.0-0034608742
- Other Identifier
- 991014877975604721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology