The endomembrane system of eukaryotic cells is essential for cellular homeostasis during growth and proliferation. Previous work showed that a central regulator of growth, namely the target of rapamycin complex 1 (TORC1), binds both membranes of vacuoles and signaling endosomes (SEs) that are distinct from multivesicular bodies (MVBs). Interestingly, the endosomal TORC1, which binds membranes in part via the EGO complex, critically defines vacuole integrity. Here, we demonstrate that SEs form at a branch point of the biosynthetic and endocytic pathways toward the vacuole and depend on MVB biogenesis. Importantly, function of the HOPS tethering complex is essential to maintain the identity of SEs and proper endosomal and vacuolar TORC1 activities. In HOPS mutants, the EGO complex redistributed to the Golgi, which resulted in a partial mislocalization of TORC1. Our study uncovers that SE function requires a functional HOPS complex and MVBs, suggesting a tight link between trafficking and signaling along the endolysosomal pathway.

中文翻译：

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HOPS 束缚复合物是维持信号内体特性和 TORC1 活性所必需的

真核细胞的内膜系统对于生长和增殖过程中的细胞稳态至关重要。先前的研究表明，生长的中央调节因子，即雷帕霉素复合物 1 (TORC1) 的靶标，与不同于多泡体 (MVB) 的液泡膜和信号内体 (SE) 结合。有趣的是，内体 TORC1 部分通过 EGO 复合物与膜结合，对液泡的完整性至关重要。在这里，我们证明 SE 是在朝向液泡的生物合成和内吞途径的分支点形成的，并且依赖于 MVB 生物发生。重要的是，HOPS 束缚复合物的功能对于维持 SE 的特性以及适当的内体和液泡 TORC1 活性至关重要。在 HOPS 突变体中，EGO 复合体重新分布到高尔基体，这导致 TORC1 部分错误定位。我们的研究发现，SE 功能需要功能性 HOPS 复合物和 MVB，这表明沿着内溶酶体途径的运输和信号传导之间存在紧密联系。