TREM2 : triggering receptor expressed on myeloid cells 2

Description

The TREM2 (triggering receptor expressed on myeloid cells 2) is a protein-coding gene located on chromosome 6.

The TREM2 gene provides instructions for making a protein called triggering receptor expressed on myeloid cells 2 (TREM2). As its name suggests, this protein is made in myeloid cells, which are cells produced in bone marrow. The TREM2 protein is found on the cell surface, where it interacts with the protein produced from the TYROBP gene. The TREM2 and TYROBP proteins form a complex that transmits chemical signals to activate the cell.The TYROBP-TREM2 complex was first identified in the immune system. This complex is involved in the growth and development of several types of immune cells, particularly dendritic cells. The TYROBP-TREM2 complex activates these cells, triggering an inflammatory response to injury or disease.The TYROBP-TREM2 complex also activates cells in the skeletal system and in the brain and spinal cord (central nervous system). In the skeletal system, the complex is found in osteoclasts, which are specialized cells that break down and remove (resorb) bone tissue that is no longer needed. These cells are involved in bone remodeling, which is a normal process that replaces old bone tissue with new bone. In the central nervous system, the TYROBP-TREM2 complex appears to play an important role in immune cells called microglia. These cells protect the brain and spinal cord from foreign invaders and remove dead nerve cells and other debris. Although the TYROBP-TREM2 complex plays a critical role in osteoclasts and microglia, its exact function in these cells is unclear

The TREM2 gene produces a protein called triggering receptor expressed on myeloid cells 2 (TREM2), also known as Triggering receptor expressed on monocytes 2. TREM2 forms a receptor signaling complex with TYROBP that mediates signaling and cell activation following ligand binding. It 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. 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. TREM2 also 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, enhancing their uptake in microglia. It binds phospholipids (preferably anionic lipids) such as phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol, and sphingomyelin. TREM2 regulates microglial proliferation by acting as an upstream regulator of the Wnt/beta-catenin signaling cascade. It is required for microglial phagocytosis of apoptotic neurons and for microglial activation and phagocytosis of myelin debris after neuronal injury and of neuronal synapses during synapse elimination in the developing brain. TREM2 regulates microglial chemotaxis and process outgrowth, and the microglial response to oxidative stress and lipopolysaccharide. It suppresses PI3K and NF-kappa-B signaling in response to lipopolysaccharide, promoting phagocytosis, suppressing pro-inflammatory cytokine and nitric oxide production, inhibiting apoptosis, and increasing expression of IL10 and TGFB. During oxidative stress, it promotes anti-apoptotic NF-kappa-B signaling and ERK signaling. TREM2 plays a role in microglial MTOR activation and metabolism and regulates age-related changes in microglial numbers. It triggers activation of the immune responses in macrophages and dendritic cells, mediates cytokine-induced formation of multinucleated giant cells formed by the fusion of macrophages, and in dendritic cells, it mediates up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival. TREM2 is involved in the positive regulation of osteoclast differentiation.

TREM2 is also known as PLOSL2, TREM-2, Trem2a, Trem2b, Trem2c.

Associated Diseases

Comprehensive carrier screening

WES Whole Exome Sequencing

Clinical Exome Sequencing