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9.B.420.  The Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Family 

TREM2 forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (Bouchon et al. 2000). 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 (Yeh et al. 2016, Zhao et al. 2018). 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 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 to enhance their uptake in microglia (Yeh et al. 2016). It also binds phospholipids (preferably anionic lipids) such as phosphatidylserine, phosphatidylglycerol and sphingomyelin (Sudom et al. 2018). It regulates microglial proliferation by acting as an upstream regulator of the Wnt/beta-catenin signaling cascade, and is required for microglial phagocytosis of apoptotic neurons (Kleinberger et al. 2014).

References associated with 9.B.420 family:

Bouchon, A., J. Dietrich, and M. Colonna. (2000). Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol 164: 4991-4995. 10799849
Karsak, M., K. Glebov, M. Scheffold, T. Bajaj, A. Kawalia, I. Karaca, S. Rading, J. Kornhuber, O. Peters, M. Diez-Fairen, L. Frölich, M. Hüll, J. Wiltfang, M. Scherer, S. Riedel-Heller, A. Schneider, M.T. Heneka, K. Fliessbach, A. Sharaf, H. Thiele, M. Lennarz, F. Jessen, W. Maier, C. Kubisch, Z. Ignatova, P. Nürnberg, P. Pastor, J. Walter, and A. Ramirez. (2020). A rare heterozygous TREM2 coding variant identified in familial clustering of dementia affects an intrinsically disordered protein region and function of TREM2. Hum Mutat 41: 169-181. 31464095
Kleinberger, G., Y. Yamanishi, M. Suárez-Calvet, E. Czirr, E. Lohmann, E. Cuyvers, H. Struyfs, N. Pettkus, A. Wenninger-Weinzierl, F. Mazaheri, S. Tahirovic, A. Lleó, D. Alcolea, J. Fortea, M. Willem, S. Lammich, J.L. Molinuevo, R. Sánchez-Valle, A. Antonell, A. Ramirez, M.T. Heneka, K. Sleegers, J. van der Zee, J.J. Martin, S. Engelborghs, A. Demirtas-Tatlidede, H. Zetterberg, C. Van Broeckhoven, H. Gurvit, T. Wyss-Coray, J. Hardy, M. Colonna, and C. Haass. (2014). TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci Transl Med 6: 243ra86. 24990881
Lok, H.C. and J.B. Kwok. (2021). The Role of White Matter Dysfunction and Leukoencephalopathy/Leukodystrophy Genes in the Aetiology of Frontotemporal Dementias: Implications for Novel Approaches to Therapeutics. Int J Mol Sci 22:. 33802612
Sudom, A., S. Talreja, J. Danao, E. Bragg, R. Kegel, X. Min, J. Richardson, Z. Zhang, N. Sharkov, E. Marcora, S. Thibault, J. Bradley, S. Wood, A.C. Lim, H. Chen, S. Wang, I.N. Foltz, S. Sambashivan, and Z. Wang. (2018). Molecular basis for the loss-of-function effects of the Alzheimer''s disease-associated R47H variant of the immune receptor TREM2. J. Biol. Chem. 293: 12634-12646. 29794134
Yeh, F.L., Y. Wang, I. Tom, L.C. Gonzalez, and M. Sheng. (2016). TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia. Neuron. 91: 328-340. 27477018
Zhao, Y., X. Wu, X. Li, L.L. Jiang, X. Gui, Y. Liu, Y. Sun, B. Zhu, J.C. Piña-Crespo, M. Zhang, N. Zhang, X. Chen, G. Bu, Z. An, T.Y. Huang, and H. Xu. (2018). TREM2 Is a Receptor for β-Amyloid that Mediates Microglial Function. Neuron. 97: 1023-1031.e7. 29518356