Nada Shigeyuki, Mori Shunsuke, Takahashi Yusuke, Okada Masato
Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Methods Enzymol. 2014;535:249-63. doi: 10.1016/B978-0-12-397925-4.00015-8.
p18/LAMTOR1 is a membrane protein specifically localized to the surface of late endosomes/lysosomes that serves as an anchor for the "Ragulator" complex, which contains p14/LAMTOR2, MP1/LAMTOR3, HBXIP, and C7orf59. The Ragulator interacts with RagAB/CD GTPases and V-ATPase and plays crucial roles for activation of mammalian target of rapamycin complex 1 (mTORC1) on the lysosomal surface. Activated mTORC1 orchestrates various cellular functions, for example, macromolecule biosynthesis, energy metabolism, autophagy, cell growth, responses to growth factors, and the trafficking and maturation of lysosomes. The Ragulator can also regulate a branch of the MAPK pathway by recruiting MEK1 to MP1/LAMTOR3. These findings suggest that p18/LAMTOR1 creates a core platform for intracellular signaling pathways that function via late endosomes/lysosomes.
p18/LAMTOR1是一种特异性定位于晚期内体/溶酶体表面的膜蛋白，它作为“Ragulator”复合物的锚定蛋白，该复合物包含p14/LAMTOR2、MP1/LAMTOR3、HBXIP和C7orf59。Ragulator与RagAB/CD GTP酶和V-ATP酶相互作用，在溶酶体表面对雷帕霉素复合物1（mTORC1）的哺乳动物靶点激活中发挥关键作用。激活的mTORC1协调各种细胞功能，例如大分子生物合成、能量代谢、自噬、细胞生长、对生长因子的反应以及溶酶体的运输和成熟。Ragulator还可通过将MEK1招募至MP1/LAMTOR3来调节MAPK途径的一个分支。这些发现表明，p18/LAMTOR1为通过晚期内体/溶酶体发挥作用的细胞内信号通路创建了一个核心平台。
