Department of Biology/Chemistry, Biochemistry Section, Osnabrück University, Osnabrück, Germany.
Department of Biology, University of Fribourg, Chemin du Musée, Fribourg, Switzerland.
J Cell Biol. 2022 May 2;221(5). doi: 10.1083/jcb.202109084. Epub 2022 Apr 9.
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.
真核细胞的内膜系统对于细胞在生长和增殖过程中的稳态至关重要。先前的工作表明，生长的一个中央调节剂，即雷帕霉素靶蛋白复合物 1（TORC1），结合液泡的双层膜和信号转导内体（SEs），而不是多泡体（MVBs）。有趣的是，通过 EGO 复合物部分结合膜的内体 TORC1，对液泡完整性起着至关重要的作用。在这里，我们证明 SEs 在朝向液泡的合成和内吞途径的分支点形成，并且依赖于 MVB 的生物发生。重要的是，HOPS 连接复合物的功能对于维持 SEs 和适当的内体和液泡 TORC1 活性的身份是必不可少的。在 HOPS 突变体中，EGO 复合物重新分布到高尔基体，导致 TORC1 的部分定位错误。我们的研究揭示了 SE 的功能需要一个功能性的 HOPS 复合物和 MVBs，这表明沿着内吞体途径运输和信号之间存在紧密联系。
