工作时Rag GTPases是一个二聚体，必须是RagA/B（ GTP）:RagC/D （GDP）一个异源二聚体方可招募mTORC1。RagA/B和RagC/D在主要功能结构域同源性非常高，一直被认为在功能上可互相替代。然而它们在N端和C端序列上差别大，提供了差异调节的基础。以往研究亮氨酸tRNA合成酶只能调节RagD，进一步提示了四个Rag蛋白...
Rag GTPases从酵母到哺乳动物高度保守。酵母中RagA或RagB的同源基因为Gtrlp; RagC或RagD的同源基因为Gtr2p。与Rag GTPases复合物相似,Gtr1p和Gtr2p也形成专性二聚体复合物。Rag GTPases通过与Ragulator复合物的相互作用将自己锚定在溶酶体上。溶酶体上同时存在能够激活mTORC1的另一个小G蛋白Rheb。Rheb的激活...
2023年12月15日,来自挪威大学的 Terje Johansen 和 Yakubu Princely Abudu 研究团队在 Molecular Cell 上发表题为 MORG1 limits mTORC1 signaling by inhibiting Rag GTPases 的文章,发现 WD结构域重复蛋白MORG1可以在营养充足条件性抑制mTORC1信号活性,促进本底水平自噬,MORG1与激活形式的Rag GTPases互作,抑制mT...
其实mTORC1本身拿到的,只是是二手消息,真正的一手消息,来自Rag GTPases 家族,包括 RagA, RagB, RagC, 和 RagD,因此mTORC1还需要通过RagC这样的蛋白来激活。 研究者们利用基因编辑技术对RagC基因一顿魔改,弄出了好几种RagC的变体,但每一种突变的方向都是增强RagC的活性,接着将这些魔改的RagC基因引入小鼠基因...
Regulation of TORC1 by Rag GTPases in nutrient response RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. The V(D)J recombination activating gene, RAG-1. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. ...
The Ragulator also functions as a guanidine exchange factor for RagA/B and connects the v-ATPase (vacuolar H þ -adenosine triphosphatase) to the Rag GTPases for mTORC1 activation by amino acids11,12. Therefore, Rag GTPases mediate amino-acid signals by recruiting the mTORC1 complex to ...
Genetic studies in Drosophila also show that Rag GTPases regulate cell growth, autophagy and animal viability during starvation. Our studies establish a function of Rag GTPases in TORC1 activation in response to amino acid signals. 展开
ARTICLERag GTPases and phosphatidylinositol 3-phosphatemediate recruitment of the AP-5/SPG11/SPG15complexJennifer Hirst 1 , Geoffrey G. Hesketh 2 , Anne-Claude Gingras 2,3 , and Margaret S. Robinson 1 Adaptor protein complex 5 (AP-5) and its partners, SPG11 and SPG15, are ...
Nutrients, such as amino acids and glucose, signal through the Rag GTPases to activate mTORC1. The GATOR1 protein complex—comprising DEPDC5, NPRL2 and NPRL3—regulates the Rag GTPases as a GTPase-activating protein (GAP) for RAGA; loss of GATOR1 desensi