Epithelial cells, such as liver-resident hepatocytes, rely heavily on the Rab family of small GTPases to perform membrane trafficking events that dictate cell physiology and metabolism. Not surprisingly, disruption of several Rab proteins can manifest in metabolic diseases or cancer. Rab32 is expressed in many secretory epithelial cells but its role in cellular metabolism is virtually unknown. In this study, we find that Rab32 associates with lysosomes and regulates proliferation and cell size of Hep3B hepatoma and HeLa cells. Specifically, we identify that Rab32 supports the mechanistic target of rapamycin complex 1 (mTORC1) signaling under basal and amino acid-stimulated conditions. Consistent with inhibited mTORC1, an increase in nuclear TFEB localization and lysosome biogenesis is also observed in Rab32-depleted cells. Finally, we find that Rab32 interacts with mTOR kinase, and that loss of Rab32 reduces the association of mTOR and mTORC1 pathway proteins with lysosomes, suggesting that Rab32 regulates lysosomal mTOR trafficking. In summary, these findings suggest that Rab32 functions as a novel regulator of cellular metabolism through supporting mTORC1 signaling.

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上皮细胞，例如驻留在肝脏的肝细胞，严重依赖小 GTP 酶的 Rab 家族来执行决定细胞生理学和代谢的膜运输事件。毫不奇怪，几种 Rab 蛋白的破坏可以在代谢疾病或癌症中体现出来。Rab32 在许多分泌上皮细胞中表达，但其在细胞代谢中的作用实际上未知。在本研究中，我们发现 Rab32 与溶酶体结合并调节 Hep3B 肝癌和 HeLa 细胞的增殖和细胞大小。具体来说，我们确定 Rab32 在基础和氨基酸刺激条件下支持雷帕霉素复合物 1 (mTORC1) 信号传导的机制靶点。与抑制 mTORC1 一致，在 Rab32 耗尽的细胞中也观察到核 TFEB 定位和溶酶体生物发生的增加。最后，我们发现 Rab32 与 mTOR 激酶相互作用，并且 Rab32 的缺失减少了 mTOR 和 mTORC1 通路蛋白与溶酶体的关联，表明 Rab32 调节溶酶体 mTOR 运输。总之，这些发现表明 Rab32 通过支持 mTORC1 信号传导作为细胞代谢的新型调节剂。

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