Trem2

GeneName

TREM2

Summary

TREM2, also known as TREM-2 or hTREM2, is a 25 kDa membrane protein primarily expressed on microglia and other immune cells in the brain. It is located in the plasma membrane and extracellular region, where it plays a critical role in immune responses, including the clearance of amyloid-beta and apoptotic cells. TREM2 functions as a receptor that binds various ligands, including lipopolysaccharides and lipoproteins, and is involved in signalling pathways that regulate microglial activation, lipid homeostasis, and neuroinflammation. Its activity is linked to the maintenance of neuronal health and the modulation of inflammatory responses in the central nervous system.

Importance

TREM2 is relevant to: - Neurodegenerative diseases, particularly Alzheimer’s disease, due to its role in amyloid-beta clearance and microglial activation - Inflammatory responses in the brain, as it regulates microglial cell activation and cytokine production - The understanding of innate immunity, given its involvement in the recognition and clearance of pathogens and apoptotic cells - The study of lipid metabolism and homeostasis, as it interacts with various lipoproteins and regulates lipid-related processes

Top Products

For researchers investigating TREM2, we highly recommend the top-selling recombinant antibody, Anti-TREM2 antibody [EPR20243] (ab209814). This antibody has been validated in knockout models, ensuring its reliability for your experiments. It is suitable for a variety of applications, particularly Western blotting (WB) and immunoprecipitation (IP), making it a versatile choice for your research needs. With 18 citations, this antibody is gaining recognition in the scientific community, reflecting its effectiveness and trustworthiness in TREM2 studies. The Recombinant Cynomolgus monkey TREM2 protein ELISA Kit (ab290833) is an excellent option for researchers looking to study TREM2 in their experiments.

Abcam Product Citation Summary

The data indicates that the Abcam antibody ab224881 is primarily used to measure TREM2 levels in cerebrospinal fluid from human patients. The studies focus on various contexts, including neurosyphilis and other related conditions, highlighting the relevance of TREM2 in neurological disorders.

Abcam Product Citation Table

Function

Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:11241283). Acts as a receptor for amyloid-beta protein 42, a cleavage product of the amyloid-beta precursor protein APP, and mediates its uptake and degradation by microglia (PubMed:27477018, PubMed:29518356). Binding to amyloid-beta 42 mediates microglial activation, proliferation, migration, apoptosis and expression of pro-inflammatory cytokines, such as IL6R and CCL3, and the anti-inflammatory cytokine ARG1 (PubMed:27477018, PubMed:29518356). Acts as a receptor for lipoprotein particles such as LDL, VLDL, and HDL and for apolipoproteins such as APOA1, APOA2, APOB, APOE, APOE2, APOE3, APOE4, and CLU and enhances their uptake in microglia (PubMed:27477018). Binds phospholipids (preferably anionic lipids) such as phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol and sphingomyelin (By similarity). Regulates microglial proliferation by acting as an upstream regulator of the Wnt/beta-catenin signaling cascade (PubMed:28077724). Required for microglial phagocytosis of apoptotic neurons (PubMed:24990881). Also required for microglial activation and phagocytosis of myelin debris after neuronal injury and of neuronal synapses during synapse elimination in the developing brain (PubMed:15728241, PubMed:25631124, PubMed:28592261, PubMed:29752066). Regulates microglial chemotaxis and process outgrowth, and also the microglial response to oxidative stress and lipopolysaccharide (PubMed:28483841, PubMed:29663649, PubMed:29859094, PubMed:30232263). It suppresses PI3K and NF-kappa-B signaling in response to lipopolysaccharide; thus promoting phagocytosis, suppressing pro-inflammatory cytokine and nitric oxide production, inhibiting apoptosis and increasing expression of IL10 and TGFB (PubMed:29663649). During oxidative stress, it promotes anti-apoptotic NF-kappa-B signaling and ERK signaling (PubMed:28592261). Plays a role in microglial MTOR activation and metabolism (PubMed:28802038). Regulates age-related changes in microglial numbers (PubMed:25631124, PubMed:29752066, PubMed:30548312). Triggers activation of the immune responses in macrophages and dendritic cells. Mediates cytokine-induced formation of multinucleated giant cells which are formed by the fusion of macrophages (PubMed:18957693). In dendritic cells, receptor of SEMA6D with PLEXNA1 as coreceptor and mediates up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival (PubMed:16715077). Involved in the positive regulation of osteoclast differentiation (PubMed:16418779).

Post-translational modifications

Undergoes ectodomain shedding through proteolytic cleavage by ADAM10 and ADAM17 to produce a transmembrane segment, the TREM2 C-terminal fragment (TREM2-CTF), which is subsequently cleaved by gamma-secretase.

Tissue Specificity

Expressed in the brain, specifically in microglia (at protein level) (PubMed:15728241, PubMed:27477018, PubMed:28077724, PubMed:28559417, PubMed:28592261, PubMed:28802038, PubMed:28855301, PubMed:29752066, PubMed:29794134). Expressed in macrophages (at protein level) (PubMed:11241283, PubMed:28559417, PubMed:28802038). Expressed at higher levels in the CNS, heart and lung than in lymph nodes or in other non-lymphoid tissues such as kidney, liver and testis (PubMed:12472885). In the CNS not all microglia express TREM2 (PubMed:12472885). Brain regions with an incomplete blood-brain barrier had the lowest percentages of TREM2 expressing microglia, whereas the lateral entorhinal and cingulate cortex had the highest percentages (PubMed:12472885).

Cellular localization

• Isoform 1
• Cell membrane
• Single-pass type I membrane protein
• Isoform 2
• Secreted

Alternative names

Trem2a, Trem2b, Trem2c, Trem2, Triggering receptor expressed on myeloid cells 2, TREM-2, Triggering receptor expressed on monocytes 2

Database links

swissprot:Q99NH8 entrezGene:83433

Other research areas

• Immunology & Infectious Disease