关键词:溶酶体+TSC复合体+结节性硬化症+乳腺癌+mTORC1 Highlights G3BPs act non-redundantly in theTSC-mTORC1 signaling axis G3BPs reside at the lysosomal surfaceand inhibit mTORC1 The TSC complex requires G3BPs as...
Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations inTSC1orTSC2, which encode proteins that negatively regulate mTOR complex 1 (mTORC1). TSC is associated with significant cognitive, psychiatric, and behavioral problems, collectively termed TSC-Associated Neuropsychiatric...
In post-mitotic neurons, Tsc1/2-mTORC1 signaling controls neuronal communication in a cell type-specific manner via regulation of membrane excitability, synaptic transmission, and synaptic plasticity6,7,8,9,10,11,12,13,14,15. Loss-of-function mutations in negative regulators of mTORC1 cause neu...
2024年8月21日,华东理工大学叶邦策,周英和浙江工业大学漆楠共同通讯在PNAS(IF=9.4)在线发表题为“The microbiota-dependent tryptophan metabolite alleviates high-fat diet–induced insulin resistance through the hepatic AhR/TSC2/mTORC1 axis”的研究论文。该研究发现,在患有糖尿病的小鼠中,与没有糖尿病的小鼠相...
研究发现,5-HIAA在HFD诱导的肠道菌群失衡下减少,并且5-HIAA能够作为AhR的配体激活下游信号传导。这一信号传导通过促进Suv39h1的泛素-蛋白酶体降解,刺激TSC2表达,从而抑制mTORC1信号传导,改善肝脏胰岛素信号传导,改善葡萄糖不耐受,并减少肥胖。 最后,该研究指出,5-HIAA可能作为治疗IR和葡萄糖不耐受特征的代谢综合征的...
内皮素-1可刺激离体心肌细胞的mtorc1活性,Ranek等人发现pkg1介导的tsc2磷酸化可以阻断这种作用。未来的研究也应该定义mtorc1下游的细胞过程,这些细胞过程有助于心脏肥大的发展。目前的研究结果表明,慢性自噬抑制和蛋白聚集物清除失败可能与此有关。 考虑到慢性mtorc1信号与多种疾病状态相关,应研究pkg1激活剂在抑制心脏...
近日,上海交通大学生命科学技术学院、微生物代谢国家重点实验室的吴更教授团队采用蛋白质结构预测与蛋白质改造设计相结合的方法,基于天然的人结节性硬化症蛋白质复合物tuberous sclerosis complex(简称TSC),改造设计了一种有着与TSC相当甚至更强的抑制Rheb与mTORC1活性、但是大小只有TSC复合物的十五分之一与九分之一的两...
Although mammalian target of rapamycin 1 (mTORC1) negatively regulates autophagy in cultured cells, how autophagy impacts mTORC1 signalling, in particular in an in vivo setting, is less clear. Here we show that autophagy supports mTORC1 hyperactivation i
Mechanistically, 5-HIAA promotes hepatic insulin signaling by directly activating AhR, which stimulates TSC2 transcription and thus inhibits mTORC1 signaling. Moreover, T2D patients exhibit decreased fecal levels of 5-HIAA. Our findings identify a noncanonical pathway of microbially producing 5-HIAA ...
实验发现,无论在ISCs细胞中还是在Villin-Cre;Tsc1f/f小鼠模型中,mTORC1蛋白在老龄小鼠肠绒毛老化过程中发挥着关键作用,而这种老化过程并非不可逆。 ✅确定mTORC1调控肠绒毛老化中的关键信号通路 研究人员通过一系列的研究,逐步明确了mTROC1-MKK6-p38MAPK-p53通路在肠绒毛老化中发挥着关键作用,并为逆转肠绒毛老化...