TMEM59 interacts with TREM2 and modulates TREM2-dependent microglial activities
TMEM59 interacts with TREM2 and modulates TREM2-dependent microglial activities
复制标题
TMEM59 与 TREM2 相互作用并调节 TREM2 依赖性小胶质细胞活动。
DOI：
10.1038/s41419-020-02874-3
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发表时间：
2020-08-13
影响因子：
9
通讯作者：
Zhang, Yun-wu
中科院分区：
文献类型：
--
作者：
Liu, Zhaoji;Ning, Jinhuan;Zhang, Yun-wu
The surface receptor triggering receptor expressed on myeloid cells 2 (TREM2) plays a crucial role in maintaining a multitude of microglial activities, such as survival, proliferation, migration, metabolism, inflammation, and phagocytosis. However, the molecular mechanisms underlying TREM2-mediated microglial activities remain largely elusive. Herein, we found that TREM2 interacted with the type I transmembrane protein TMEM59, whose expression could facilitate autophagic flux through its carboxyl-terminus. TMEM59 expression was decreased upon lipopolysaccharide treatment. While downregulation of TMEM59 promoted anti-inflammatory factor expression and attenuated lipopolysaccharide treatment-induced inflammation. Importantly, we found that overexpression of TREM2 reduced TMEM59 protein levels through promoting its degradation, whereas TMEM59 levels were elevated in Trem2-deficient microglia. Finally, impaired survival, proliferation, migration, and phagocytosis, as well as dysregulated autophagy and metabolism in Trem2-deficient microglia were attenuated upon TMEM59 silencing. Together, our findings reveal a novel function of TREM2 in mediating TMEM59 protein degradation and demonstrate the importance of TMEM59 homeostasis in maintaining TREM2-mediated microglial activities.
