Intracellular trafficking of TREM2 is regulated by presenilin 1.
Intracellular trafficking of TREM2 is regulated by presenilin 1.
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DOI：
10.1038/emm.2017.200
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发表时间：
2017-12-01
影响因子：
12.8
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Zhao Y;Li X;Huang T;Jiang LL;Tan Z;Zhang M;Cheng IH;Wang X;Bu G;Zhang YW;Wang Q;Xu H
Genetic mutations in triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to a variety of neurodegenerative diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia and Parkinson’s disease. In the brain, TREM2 is highly expressed on the cell surface of microglia, where it can transduce signals to regulate microglial functions such as phagocytosis. To date, mechanisms underlying intracellular trafficking of TREM2 remain elusive. Mutations in the presenilin 1 (PS1) catalytic subunit of the γ-secretase complex have been associated with increased generation of the amyloidogenic Aβ (amyloid-β) 42 peptide through cleavage of the Aβ precursor amyloid precursor protein. Here we found that TREM2 interacts with PS1 in a manner independent of γ-secretase activity. Mutations in TREM2 alter its subcellular localization and affects its interaction with PS1. Upregulation of PS1 reduces, whereas downregulation of PS1 increases, steady-state levels of cell surface TREM2. Furthermore, PS1 overexpression results in attenuated phagocytic uptake of Aβ by microglia, which is reversed by TREM2 overexpression. Our data indicate a novel role for PS1 in regulating TREM2 intracellular trafficking and pathophysiological function.
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影响因子：
4.2
作者：
Forabosco P;Ramasamy A;Trabzuni D;Walker R;Smith C;Bras J;Levine AP;Hardy J;Pocock JM;Guerreiro R;Weale ME;Ryten M
通讯作者：
Ryten M
DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
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;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
7.7
作者：
Kober, Daniel L.;Alexander-Brett, Jennifer M.;Brett, Thomas J.
通讯作者：
Brett, Thomas J.
影响因子：
4.2
作者：
Borroni, Barbara;Ferrari, Francesca;Padovani, Alessandro
通讯作者：
Padovani, Alessandro