The chemerin receptor CMKLR1 is a functional receptor for amyloid-β peptide
Peng L.2; Yu Y.2; Liu J.2; Li S.2; He H.2; Cheng N.1; Ye R.D.2
Source PublicationJournal of Alzheimer's Disease
ISSN18758908 13872877
AbstractAmyloid-β peptides such as Aβ (Aβ) play a pivotal role in the progression of Alzheimer's disease (AD). Aβ is neurotoxic and can activate microglial cells. These cells in turn migrate toward senile (neuritic) plaques and help to clear Aβ deposits through an endocytotic mechanism. It is of potential significance to characterize the Aβ receptors that mediate microglia chemotaxis and Aβ uptake. We found that the transcript of the chemerin receptor CMKLR1 was upregulated in the brain of AD patients and in mouse brain tissue following systemic LPS administration. CMKLR1 and Aβ colocalized in hippocampus and cortex of AβPP/PS1 transgenic mice. Moreover, Aβ bound specifically to CMKLR1 in stably transfected rat basophilic leukemia (RBL) cells (CMKLR1-RBL), suggesting that CMKLR1 is a receptor for Aβ. Aβ induced migration of primary microglia, the mouse microglial cell line N9, and CMKLR1-RBL cells, but not untransfected RBL-2H3 cells. Mechanistic studies showed that Aβ induced CMKLR1-dependent cell migration through activation of the ERK1/2, PKA, and Akt pathways, but not Ca mobilization. Aβ stimulation of CMKLR1-RBL cells and primary glial cells led to internalization of the Aβ-CMKLR1 complex, suggesting a potential role for CMKLR1 in Aβ clearance. Taken together, these results indicate that Aβ activates CMKLR1, leading to glia cell migration and clearance of Aβ. CMKLR1 is a new addition to the repertoire of cell surface molecules that are responsible for Aβ processing and clearance.
KeywordAlzheimer's disease amyloid-β chemerin receptor chemotaxis microglial cells
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Cited Times [WOS]:24   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.University of Illinois College of Medicine
2.Shanghai Jiao Tong University
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GB/T 7714
Peng L.,Yu Y.,Liu J.,et al. The chemerin receptor CMKLR1 is a functional receptor for amyloid-β peptide[J]. Journal of Alzheimer's Disease,2014,43(1):227-242.
APA Peng L..,Yu Y..,Liu J..,Li S..,He H..,...&Ye R.D..(2014).The chemerin receptor CMKLR1 is a functional receptor for amyloid-β peptide.Journal of Alzheimer's Disease,43(1),227-242.
MLA Peng L.,et al."The chemerin receptor CMKLR1 is a functional receptor for amyloid-β peptide".Journal of Alzheimer's Disease 43.1(2014):227-242.
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