Varlakhanova Natalia V, Mihalevic Michael J, Bernstein Kara A, Ford Marijn G J
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, 3500 Terrace Street, Pittsburgh, PA 15261, USA.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
J Cell Sci. 2017 Nov 15;130(22):3878-3890. doi: 10.1242/jcs.207910. Epub 2017 Oct 9.
The TORC1 complex is a key regulator of cell growth and metabolism in The vacuole-associated EGO complex couples activation of TORC1 to the availability of amino acids, specifically glutamine and leucine. The EGO complex is also essential for reactivation of TORC1 following rapamycin-induced growth arrest and for its distribution on the vacuolar membrane. Pib2, a FYVE-containing phosphatidylinositol 3-phosphate (PI3P)-binding protein, is a newly discovered and poorly characterized activator of TORC1. Here, we show that Pib2 is required for reactivation of TORC1 following rapamycin-induced growth arrest. Pib2 is required for EGO complex-mediated activation of TORC1 by glutamine and leucine as well as for redistribution of Tor1 on the vacuolar membrane. Therefore, Pib2 and the EGO complex cooperate to activate TORC1 and connect phosphoinositide 3-kinase (PI3K) signaling and TORC1 activity.
TORC1复合物是细胞生长和代谢的关键调节因子。液泡相关的EGO复合物将TORC1的激活与氨基酸（特别是谷氨酰胺和亮氨酸）的可用性联系起来。EGO复合物对于雷帕霉素诱导的生长停滞后TORC1的重新激活及其在液泡膜上的分布也至关重要。Pib2是一种含FYVE结构域的磷脂酰肌醇3-磷酸（PI3P）结合蛋白，是新发现的且特性了解较少的TORC1激活剂。在此，我们表明Pib2是雷帕霉素诱导的生长停滞后TORC1重新激活所必需的。Pib2是EGO复合物介导的谷氨酰胺和亮氨酸对TORC1激活以及Tor1在液泡膜上重新分布所必需的。因此，Pib2和EGO复合物协同激活TORC1，并连接磷酸肌醇3-激酶（PI3K）信号传导和TORC1活性。
