Lysosomal signaling facilitates the migration of immune cells by releasing Ca2+ to activate the actin-based motor myosin II at the cell rear. However, how the actomyosin cytoskeleton physically associates to lysosomes is unknown. We have previously identified myosin II as a direct interactor of Rab7b, a small GTPase that mediates the transport from late endosomes/lysosomes to the trans-Golgi network (TGN). Here, we show that Rab7b regulates the migration of dendritic cells (DCs) in one- and three-dimensional environments. DCs are immune sentinels that transport antigens from peripheral tissues to lymph nodes to activate T lymphocytes and initiate adaptive immune responses. We found that the lack of Rab7b reduces myosin II light chain phosphorylation and the activation of the transcription factor EB (TFEB), which controls lysosomal signaling and is required for fast DC migration. Furthermore, we demonstrate that Rab7b interacts with the lysosomal Ca2+ channel TRPML1 (also known as MCOLN1), enabling the local activation of myosin II at the cell rear. Taken together, our findings identify Rab7b as the missing physical link between lysosomes and the actomyosin cytoskeleton, allowing control of immune cell migration through lysosomal signaling. This article has an associated First Person interview with the first author of the paper.

中文翻译：

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Rab7b 通过将溶酶体连接到肌动球蛋白细胞骨架来调节树突状细胞迁移。

溶酶体信号通过释放 Ca2+ 来激活细胞后部的基于肌动蛋白的运动肌球蛋白 II，从而促进免疫细胞的迁移。然而，肌动球蛋白细胞骨架如何与溶酶体物理结合尚不清楚。我们之前已将肌球蛋白 II 鉴定为 Rab7b 的直接相互作用物，Rab7b 是一种小型 GTP 酶，可介导从晚期内体/溶酶体到跨高尔基网络 (TGN) 的转运。在这里，我们展示了 Rab7b 在一维和三维环境中调节树突状细胞 (DC) 的迁移。DC是免疫哨兵，将抗原从外周组织转运到淋巴结以激活T淋巴细胞并启动适应性免疫反应。我们发现 Rab7b 的缺乏会降低肌球蛋白 II 轻链的磷酸化和转录因子 EB (TFEB) 的激活，它控制溶酶体信号传导，是快速 DC 迁移所必需的。此外，我们证明 Rab7b 与溶酶体 Ca2+ 通道 TRPML1（也称为 MCOLN1）相互作用，从而能够在细胞后部局部激活肌球蛋白 II。总之，我们的研究结果将 Rab7b 确定为溶酶体和肌动球蛋白细胞骨架之间缺失的物理联系，从而允许通过溶酶体信号传导控制免疫细胞迁移。本文与论文的第一作者进行了相关的第一人称采访。允许通过溶酶体信号控制免疫细胞迁移。本文与论文的第一作者进行了相关的第一人称采访。允许通过溶酶体信号控制免疫细胞迁移。本文与论文的第一作者进行了相关的第一人称采访。