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Gene Review

TREM2  -  triggering receptor expressed on myeloid...

Homo sapiens

Synonyms: TREM-2, Trem2a, Trem2b, Trem2c, Triggering receptor expressed on monocytes 2, ...
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Disease relevance of TREM2


Psychiatry related information on TREM2

  • Distribution and signaling of TREM2/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementia [1].
  • Recently, it has been shown that genetic defects of human DAP12/KARAP and TREM-2 result in a rare syndrome characterized by bone cysts and presenile dementia called Nasu-Hakola disease [5].

High impact information on TREM2


Biological context of TREM2

  • Surface expression of TREM2, low in resting CHME-5 and T98G cells, increases significantly and transiently (60 min) when cells are stimulated by ionomycin, as revealed by both surface biotinylation and surface immunolabeling [1].
  • Recently, molecular analysis of affected families revealed mutations in the DAP12 (TYROBP) or TREM2 genes, providing an interesting example how mutations in two different subunits of a multi-subunit receptor complex result in an identical human disease phenotype [7].
  • Two healthy subjects heterozygous for one mutated TREM2 allele showed a deficit of visuospatial memory associated with hypoperfusion in the basal ganglia, whereas the homozygotes for the wild-type allele of TREM2 did not show any abnormalities [8].
  • TREM2 RNA interference (RNAi) was used to disrupt expression of TREM2 in pre-osteoclasts [9].
  • Moreover, mutation scanning of the five exons of TREM2 failed to detect the presence of novel polymorphisms [10].

Anatomical context of TREM2

  • TREM2 forms a receptor signaling complex with TYROBP and triggers activation of the immune responses in macrophages and dendritic cells [11].
  • Our results provide the first information about the expression, distribution (mostly intracellular) and functioning of TREM2/DAP12 system in nerve cells, a necessary step in the understanding of the cellular mechanisms affected in polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy [1].
  • Also, the possible roles of the DAP12/TREM2 signaling pathway in microglia and osteoclasts in humans are just beginning to be elucidated [7].
  • In addition to triggering receptor expressed on myeloid cells (TREM)-1 and TREM2, the cluster contains NKp44, a triggering receptor whose expression is limited to NK cells [12].
  • TREM1 and TREM2 activate myeloid cells by signalling through the adaptor protein DAP12 [4].

Analytical, diagnostic and therapeutic context of TREM2

  • We performed a functional neuroimaging (99mTc-ECD SPECT) and neuropsychological study of healthy members of an Italian family carrying a mutation in the TREM2 gene [8].
  • MATERIALS AND METHODS: We generated monoclonal anti-mouse TREM2 antibodies (mAb), analyzed pre-osteoclasts and mature OCs for TREM2 surface expression, and determined the effect of antibody ligation on in vitro OC differentiation, resorption, and migration [9].


  1. Distribution and signaling of TREM2/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementia. Sessa, G., Podini, P., Mariani, M., Meroni, A., Spreafico, R., Sinigaglia, F., Colonna, M., Panina, P., Meldolesi, J. Eur. J. Neurosci. (2004) [Pubmed]
  2. DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features. Paloneva, J., Mandelin, J., Kiialainen, A., Bohling, T., Prudlo, J., Hakola, P., Haltia, M., Konttinen, Y.T., Peltonen, L. J. Exp. Med. (2003) [Pubmed]
  3. The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2. Bianchin, M.M., Lima, J.E., Natel, J., Sakamoto, A.C. Neurology (2006) [Pubmed]
  4. TREMs in the immune system and beyond. Colonna, M. Nat. Rev. Immunol. (2003) [Pubmed]
  5. Impaired differentiation of osteoclasts in TREM-2-deficient individuals. Cella, M., Buonsanti, C., Strader, C., Kondo, T., Salmaggi, A., Colonna, M. J. Exp. Med. (2003) [Pubmed]
  6. Cutting edge: Inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. Hamerman, J.A., Jarjoura, J.R., Humphrey, M.B., Nakamura, M.C., Seaman, W.E., Lanier, L.L. J. Immunol. (2006) [Pubmed]
  7. Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy--PLOSL): a dementia associated with bone cystic lesions. From clinical to genetic and molecular aspects. Bianchin, M.M., Capella, H.M., Chaves, D.L., Steindel, M., Grisard, E.C., Ganev, G.G., da Silva Júnior, J.P., Neto Evaldo, S., Poffo, M.A., Walz, R., Carlotti Júnior, C.G., Sakamoto, A.C. Cell. Mol. Neurobiol. (2004) [Pubmed]
  8. Neuropsychological tests and functional nuclear neuroimaging provide evidence of subclinical impairment in Nasu-Hakola disease heterozygotes. Montalbetti, L., Ratti, M.T., Greco, B., Aprile, C., Moglia, A., Soragna, D. Funct. Neurol. (2005) [Pubmed]
  9. TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. Humphrey, M.B., Daws, M.R., Spusta, S.C., Niemi, E.C., Torchia, J.A., Lanier, L.L., Seaman, W.E., Nakamura, M.C. J. Bone Miner. Res. (2006) [Pubmed]
  10. Absence of TREM2 polymorphisms in patients with Alzheimer's disease and Frontotemporal Lobar Degeneration. Fenoglio, C., Galimberti, D., Piccio, L., Scalabrini, D., Panina, P., Buonsanti, C., Venturelli, E., Lovati, C., Forloni, G., Mariani, C., Bresolin, N., Scarpini, E. Neurosci. Lett. (2007) [Pubmed]
  11. Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Tranebjaerg, L., Konttinen, Y., Peltonen, L. Am. J. Hum. Genet. (2002) [Pubmed]
  12. The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44. Allcock, R.J., Barrow, A.D., Forbes, S., Beck, S., Trowsdale, J. Eur. J. Immunol. (2003) [Pubmed]
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