The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E.

Abstract

The triggering receptor expressed on myeloid cells 2 (TREM2) is an Ig-like V-type receptor expressed by populations of myeloid cells in the central nervous system and periphery. Loss-of-function mutations in TREM2 cause a progressive, fatal neurodegenerative disorder called Nasu-Hakola disease. In addition, a TREM2 R47H coding variant was recently identified as a risk factor for late-onset Alzheimer disease. TREM2 binds various polyanionic molecules but no specific protein ligands have been identified. Here we show that TREM2 specifically binds apolipoprotein E, a well established participant in Alzheimer disease. TREM2-Ig fusions efficiently precipitate ApoE from cerebrospinal fluid and serum. TREM2 also binds recombinant ApoE in solution and immobilized ApoE as detected by ELISA. Furthermore, the Alzheimer disease-associated R47H mutation, and other artificial mutations introduced in the same location, markedly reduced the affinity of TREM2 for ApoE. These findings reveal a link between two Alzheimer disease risk factors and may provide important clues to the pathogenesis of Nasu-Hakola disease and other neurodegenerative disorders.

• Authors: Charles C Bailey, Lindsey B DeVaux, Michael Farzan
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 43 Pg. 26033-42 (Oct 23 2015) ISSN: 1083-351X [Electronic] United States
• PMID: 26374897 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Apolipoproteins E
• Immunoglobulins
• Membrane Glycoproteins
• Receptors, Immunologic
• TREM2 protein, human

Topics

• Apolipoproteins E (cerebrospinal fluid, metabolism)
• Humans
• Immunoglobulins (metabolism)
• Jurkat Cells
• Lipid Metabolism
• Membrane Glycoproteins (metabolism)
• Neurodegenerative Diseases (metabolism)
• Protein Binding
• Receptors, Immunologic (metabolism)