TY - JOUR
T1 - Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival
AU - Meucci, Olimpia
AU - Fatatis, Alessandro
AU - Simen, Arthur A.
AU - Miller, Richard J.
PY - 2000/7/5
Y1 - 2000/7/5
N2 - 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 pro- survival 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 gp120(IIIB), 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.
AB - 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 pro- survival 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 gp120(IIIB), 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.
UR - http://www.scopus.com/inward/record.url?scp=0034608742&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034608742&partnerID=8YFLogxK
U2 - 10.1073/pnas.090017497
DO - 10.1073/pnas.090017497
M3 - Article
C2 - 10869418
AN - SCOPUS:0034608742
SN - 0027-8424
VL - 97
SP - 8075
EP - 8080
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 14
ER -