TREM2

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Triggering receptor expressed on myeloid cells 2
Identifiers
Symbols TREM2 ; TREM-2; Trem2a; Trem2b; Trem2c
External IDs OMIM605086 MGI1913150 HomoloGene10352 GeneCards: TREM2 Gene
RNA expression pattern
PBB GE TREM2 219725 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 54209 83433
Ensembl ENSG00000095970 ENSMUSG00000023992
UniProt Q9NZC2 Q99NH8
RefSeq (mRNA) NM_001271821 NM_001272078
RefSeq (protein) NP_001258750 NP_001259007
Location (UCSC) Chr 6:
41.13 – 41.13 Mb
Chr 17:
48.35 – 48.35 Mb
PubMed search [1] [2]

Triggering receptor expressed on myeloid cells 2 is a protein that in humans is encoded by the TREM2 gene.[1][2][3]

Function[edit]

Monocyte/macrophage- and neutrophil-mediated inflammatory responses can be stimulated through a variety of receptors, including G protein-linked 7-transmembrane receptors (e.g., FPR1), Fc receptors, CD14 and Toll-like receptors (e.g., TLR4), and cytokine receptors (e.g., IFNGR1). Engagement of these receptors can also prime myeloid cells to respond to other stimuli. Myeloid cells express receptors belonging to the Ig superfamily, such as TREM2, or to the C-type lectin superfamily. Depending on their transmembrane and cytoplasmic sequence structure, these receptors have either activating (e.g., KIR2DS1) or inhibitory functions (e.g., KIR2DL1).[3]

Clinical significance[edit]

Homozygous mutations in TREM2 are known to cause rare, autosomal recessive forms of dementia with an early onset and presenting with [2] or without [4] bone cysts and fractures.

A rare missense mutation (rs75932628-T) in the gene encoding TREM2, (predicted to result in an R47H substitution), confers a significant risk of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, it is suspected of interfering with the brain’s ability to prevent the buildup of plaque.[5][6][7]

References[edit]

  1. ^ Bouchon A, Dietrich J, Colonna M (Jun 2000). "Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes". J Immunol 164 (10): 4991–5. PMID 10799849. 
  2. ^ a b 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 (Aug 2002). "Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype". Am J Hum Genet 71 (3): 656–62. doi:10.1086/342259. PMC 379202. PMID 12080485. 
  3. ^ a b "Entrez Gene: TREM2 triggering receptor expressed on myeloid cells 2". 
  4. ^ Guerreiro RJ, Lohmann E, Brás JM, Gibbs JR, Rohrer JD, Gurunlian N, Dursun B, Bilgic B, Hanagasi H, Gurvit H, Emre M, Singleton A, Hardy J (January 2013). "Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement". JAMA Neurol 70 (1): 78–84. doi:10.1001/jamaneurol.2013.579. PMID 23318515. 
  5. ^ Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, Hazrati L, Collinge J, Pocock J, Lashley T, Williams J, Lambert JC, Amouyel P, Goate A, Rademakers R, Morgan K, Powell J, St George-Hyslop P, Singleton A, Hardy J (January 2013). "TREM2 variants in Alzheimer's disease". N. Engl. J. Med. 368 (2): 117–27. doi:10.1056/NEJMoa1211851. PMC 3631573. PMID 23150934. 
  6. ^ Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, Bjornsson S, Huttenlocher J, Levey AI, Lah JJ, Rujescu D, Hampel H, Giegling I, Andreassen OA, Engedal K, Ulstein I, Djurovic S, Ibrahim-Verbaas C, Hofman A, Ikram MA, van Duijn CM, Thorsteinsdottir U, Kong A, Stefansson K (January 2013). "Variant of TREM2 associated with the risk of Alzheimer's disease". N. Engl. J. Med. 368 (2): 107–16. doi:10.1056/NEJMoa1211103. PMC 3677583. PMID 23150908. 
  7. ^ Kolata G (14 November 2012). "Alzheimer’s Tied to Mutation Harming Immune Response". New York Times. Retrieved 15 November 2012. 

External links[edit]

Further reading[edit]