Contents

Search

triggering receptor expressed on myeloid cells 2; triggering receptor expressed on monocytes 2 (TREM2)

Function: - possible role in chronic inflammatory conditions - may stimulate production of constitutive rather than inflammatory chemokines & cytokines - forms a receptor signaling complex with TYROBP (TYRO protein tyrosine kinase binding protein); activating immune responses in macrophages & dendritic cells - associates with DAP12 for its signaling function - LILRB2 mediates TREM2 signaling [6] - RHOH & NCK2 encode signaling molecules downstream from TREM2 that influence cytoskeletal rearrangement of microglia - has both exogenous ligands on pathogens & endogenous ligands - Hsp60 is appears to be an agonist of TREM2 - an endogenous ligand may be present on dendritic cells - activation of TREM2 may stimulate - proliferation of CD4-positive T-cells - secretion of TNF & CCL2 - TREM2 may have anti-inflammatory function(s) via inhibition of Toll-like receptor(s) - TREM2 can inhibit maturation of dendritic cells - TREM2 can inhibit type I interferon responses - TREM2 can inhibit induction of antigen-specific T-cell proliferation Compartment: - isoform 1: cell membrane - isoforms 2,3: secreted Alternative splicing: named isoforms=3 Expression: - macrophages - dendritic cells - osteoclasts - NOT found on granulocytes or monocytes - expressed on myeloid cells in CSF & as soluble TREM2 in CSF [5] - in the CNS, expressed on microglia - expressed throughout the CNS, especially in white matter - strongest expression in the basal ganglia, corpus callosum, medulla oblongata & spinal cord - expression rises in parallel with expression of beta-amyloid in the cerebral cortex [4] - TREM2 is overexpressed in subtype 1 (hyperplastic subtype) of Alzheimer's disease [6] Polymorphism: - TREM2 variant rs75932628 confers a 3-fold increase in risk for Alzheimer's disease [4] - increased risk attributed to diminished function of TREM2 Pathology: - CSF soluble TREM2 & TREM2 expressed on microglia may play a role in facilitation of PHF-tau propagation by activated microglia in association with beta-amyloid [5] - defects in TREM2 or TYROBP genes associated with presenile dementia with bone cysts

Related

polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), presenile dementia with bone cysts; Nasu-Hakola disease

General

triggering receptor expressed on myeloid cells

Properties

SIZE: MW = 25 kD entity length = 230 aa MOTIF: signal sequence {1-18} N-glycosylation site {N20} immunoglobulin superfamily domain {29-112} MOTIF: cysteine residue {C36} MODIFICATION: cysteine residue {C110} cysteine residue {C51} MODIFICATION: cysteine residue {C60} cysteine residue {C60} MODIFICATION: cysteine residue {C51} N-glycosylation site {N79} cysteine residue {C110} MODIFICATION: cysteine residue {C36} transmembrane domain {175-195}

Database Correlations

OMIM correlations MORBIDMAP 605086 UniProt Q9NZC2 Pfam PF07686 Entrez Gene 54209

References

  1. OMIM :accession 605086
  2. Entrez Gene :accession 54209
  3. UniProt :accession Q9NZC2
  4. Jonsson T et al Variant of TREM2 Associated with the Risk of Alzheimer's Disease N Engl J Med. November 14, 2012 PMID: 23150908 http://www.nejm.org/doi/full/10.1056/NEJMoa1211103 - Guerreiro R et al TREM2 Variants in Alzheimer's Disease N Engl J Med. November 14, 2012 PMID: 23150934 http://www.nejm.org/doi/full/10.1056/NEJMoa1211851
  5. Pascoal TA, Benedet AL, Ashton NJ et al. Microglial activation and tau propagate jointly across Braak stages. Nat Med 2021. August 21 PMID: 34446931 https://www.nature.com/articles/s41591-021-01456-w
  6. Tims BM, Vromen EM, Mjaavatten O et al Cerebrospinal fluid proteomics in patients with Alzheimer's disease reveals five molecular subtypes with distinct genetic risk profiles. Nat Aging. 2024 Jan;4(1):33-47. PMID: 38195725 PMCID: PMC10798889 Free PMC article. https://www.nature.com/articles/s43587-023-00550-7