ATP6V0d2 mediates leucine-induced mTORC1 activation and polarization of macrophages

• 作者: Arian Laurence Feili Gong Guoyu Bi Huabin Li Jing Luo Na Liu Pingfei Li Xiang-Ping Yang Xiaofei Deng Yufei Chen Zhengping Wei
• 来源期刊: 蛋白质与细胞
• 年，卷（期）: 2019,（8）
• 所属期刊栏目: LETTERS
• 页码范围: 615-619
• 页数: 5页
• 语种: 英文

摘要

Dear Editor, mTORC1, as a center regulatory hub of metabolism, senses the cellular energy status, nutrition and extracellular stimuli and regulates cell growth, differentiation and functions of immune cells (Powell et al., 2012). Lysosomal localization of key signal components is critical for mTORC1 activation:mTORC1 activation requires co-localization of activated Rheb and mTORC1 to the lysosome membrane (Buerger et al., 2006). Signals including growth factors, cellular stresses and energy levels act on the disruption the forma-tion of tuberous sclerosis complex (TSC) complex, com-prised of TSC1, TSC2 and TBC1D7, which leads to the translocation and activation of Rheb on the lysosome membrane (Dibble et al., 2012). In response to nutrient levels, specifically the availability of amino acids and glucose (Efeyan et al., 2013), mTORC1 is recruited to the lysosomal surface by Rag GTPases that are heterodimers of RagA or RagC bound to RagB or RagD. Multiple protein complexes have been implicated in regulation of mTORC1 upon nutrient sensing including Ragulator, GATOR1, GATOR2, KICSTOR and vacuolar ATPases (Wolfson et al., 2017). Vacuolar ATPases are large multiple-protein complexes that acidify the lysosome and may mediate additional functions inde-pendent of their proton pump activity (Nishi and Forgac, 2002).